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Enzyme Nomenclature
Information on EC 2.7.11.26 - tau-protein kinase
for references in articles please use BRENDA:EC2.7.11.26
Word Map on EC 2.7.11.26
- 2.7.11.26
- diabetes
- aicar
- obesity
-
carboxylase
- rapamycin
- injury
- metformin
- dysfunction
- peroxisome
- cardiac
- inflammation
-
proliferator-activated
- endothelial
- acetyl-coa
- alzheimer
- adipose
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autophagy
- adipocytes
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mitogen-activated
-
mapks
- triglyceride
-
high-fat
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adiponectin
-
3-kinase
-
obese
- phosphatidylinositol
-
signal-regulated
-
leptin
- myotubes
-
insulin-stimulated
-
diet-induced
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hyperphosphorylation
- cardiomyocytes
-
mtorc1
- hypothalamic
-
antidiabetic
-
element-binding
-
lipogenesis
- lithium
-
stress-activated
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cardioprotective
-
beta-catenin
-
lipogenic
-
sirtuins
-
rho-associated
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necroptosis
-
receptor-interacting
- biguanide
-
monophosphate-activated
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hfd-induced
- pharmacology
- medicine
- drug development
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.7.11.26
-
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RECOMMENDED NAME
GeneOntology No.
tau-protein kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + tau-protein = ADP + O-phospho-tau-protein
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ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
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-
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ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
activation loop structure, substrate binding structure, and catalytic site structure and mechanism
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ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
glycogen synthase kinase-3beta also performs serine/threonine protein kinase reaction, EC 2.7.11.1, with other substrates than tau, e.g. it phosphorylates the glycogen synthase
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ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
GSK-3 and PKA catalyze tau phosphorylation in the brain, while GSK-3 performs phosphorylation of glycogen synthase, EC 2.7.11.1, and other proteins in different tissues, and PKA performs phosphorylation of other proteins in different tissues
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:[tau-protein] O-phosphotransferase
Activated by tubulin. Involved in the formation of paired helical filaments, which are the main fibrous component of all fibrillary lesions in brain and are associated with Alzheimer's disease.
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CAS REGISTRY NUMBER
COMMENTARY
111694-09-8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
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491056, 491676, 491679, 491683, 491710, 702587, 702637, 705224, 739843, 739962, 740125, 740530, 740531, 741409
SwissProt
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660602, 662134, 662152, 662261, 662313, 662388, 662674, 662690, 662855, 662870, 677380, 681536, 691083, 691623, 701940, 702438, 702646, 703016, 703599, 704555, 704616, 704796, 704801, 704992, 705240, 705246, 705263, 705280, 705325, 705326, 705328, 705412, 705440, 705796, 705824, 705916, 706016, 706672, 741395
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662124, 662688, 662855, 681529, 693719, 693755, 702965, 703720, 703929, 703941, 704607, 705282, 705285, 705327, 705455, 705824, 705911, 706424
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mouse, brain TTK cDNA nucleotide sequence, same accession number in EMBL/DDBJ
SwissProt
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
TTBK2 is a serine/threonine protein kinase of the CK1 superfamily
evolution
TTBK2 is a serine/threonine protein kinase of the CK1 superfamily
evolution
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sequence comparisons of diverse protein kinases, phylogenetic tree of tau protein kinases and analysis
malfunction
-
inhibition of glycogen synthase kinase-3 increases beta-catenin concentration in the cytoplasm
malfunction
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inhibition of GSK-3beta mediates Nrf2 activation by the M1 receptor
malfunction
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inactivation of glycogen synthase kinase-3beta suppresses mitochondrial permeability transition pore opening and protects cardiomyocytes
malfunction
-
GSK-3beta heterozygote mice, which express GSK-3beta at 50% wild type levels, have impaired memory reconsolidation but normal memory consolidation
malfunction
-
inhibition of GSK-3beta abrogates glucocorticoid-induced bone loss by increasing beta-catenin- and Runx2-mediated osteoblast differentiation
malfunction
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the deletion of the C-terminal tail of slicing variant GSK-3beta2 results in considerable reduction of tau phosphorylation activity as compared with GSK-3beta1
malfunction
mutations of TTBK2 are associated with spinocerebellar ataxia type 11. Mutation of TTBK2 may potentially be more serious than mutations of other proteins involved in ciliopathies. Upregulated TTBK2 in kidney carcinoma and melanoma cell lines is correlated with resistance of the target therapeutic drug Sunitinib, while knockdown of TTBK2 in these cells increases Sunitinib sensitivity. Reduction of TTBK2 also increases Sunitinib inhibition of cancer cell migration. The enzyme phosphorylates transactive response (TAR) DNA-binding protein 43, or TDP-43, a DNA/RNA binding protein responsible for transcriptional repression, pre-mRNA splicing, and translational regulation. Hyperphosphorylation-associated aggregation of TDP-43 is a signature of two neurodegenerative diseases: amyotrophic sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Phosphorylation of TDP-43 by both TTBK1 and TTBK2 overexpression results in relocalization of TDP-43 from the nucleus to the cytosol. TTBK1/TTBK2 colocalize with phospho-TDP-43 in the frontal cortex of FTLD-TDP patients and in the spinal cord of ALS patients, suggesting that phosphorylation of TDP-43 by both TTBK1 and TTBK2 likely plays a role in progression of these diseases
malfunction
knockout TTBK2fmly1/fmly1 mice with homozygous mutants of truncated TTBK2 at residue 450 are embryonic lethal at embryonic day 10, with indistinct brain subdivisions, distorted caudal bodies, and delayed body and brain development. Heterozygous mutant TTBK2fmly1/+ mice are completely normal and exhibit a regular lifespan
malfunction
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abnormal tau phosphorylation (p-tau) occurs after hypoxic damage to the brain associated with traumatic brain injury and stroke
malfunction
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tau-tubulin kinase 1 enhances prefibrillar tau aggregation, forming small oligomers, and motor neuron degeneration in P301L FTDP-17 tau-mutant mice. TTBK1 up-regulation enhances tau phosphorylation and oligomerization, whose toxicity results in enhanced neurodegeneration and locomotor dysfunction in a tauopathy animal model, overview. The bigenic mice show enhanced tau phosphorylation at multiple sites, i.e. AT8, 12E8, PHF-1, and pS422, and they show significant locomotor dysfunction as determined by both rotorod and grip strength tests, as well as enhanced loss of motor neurons in the L4-L5 spinal cord. The neuronal dysfunction and degeneration is associated with increased levels of tau oligomers, cyclin-dependent protein kinase 5 activators p35 and p25, and pY216 phosphorylated glycogen synthase kinase 3-beta
malfunction
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comparison of phosphorylation sites in human Alzheimer and control brain with recombinant tau phosphorylated by GSK-3 in vitro, several sites are not phosphrylated in Alzheimer's disease samples, overview. Inhibiting GSK-3 with SB-415286 also protects cultured neurons from cell death induced by reduced phosphatidylinositol 3-kinase activity, and this protection is paralleled by decreased tau phosphorylation
malfunction
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the abnormal phosphorylation of tau leads to the formation of neurofibrillary tangles produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia
malfunction
deletion of the C-terminus alphaDELTACT-4 leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling, GSK-3 C-terminal deletions mutants fail to interact with axin GID; deletion of the C-terminus betaDELTACT-4 leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling, GSK-3 C-terminal deletions mutants fail to interact with axin GID
malfunction
phosphorylation of CRMP2, CRMP4, beta-catenin, c-Myc, c-Jun and some residues on tau associated with Alzheimer's disease, is altered in cortical tissue lacking both isoforms of GSK3; phosphorylation of CRMP2, CRMP4, beta-catenin, c-Myc, c-Jun and some residues on tau associated with Alzheimer's disease, is altered in cortical tissue lacking both isoforms of GSK3
malfunction
functional status of glycogen synthase kinase-3 and correlated appearance of distinct tau phospho-epitopes: neurons displaying increases in activation of phosphorylation of glycogen synthase kinase-3alpha/beta at tyrosine 279/216 also show an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. These neurons are rare in 8.5-month-old, but numerous in 18.5- and 28-month-old pR5 mice. Tau- rather than an amyloid-beta peptide-induced pathology is associated with increased neuronal tyrosine phosphorylation. Tyrosine phosphorylation only increases in neurons with fibrillar tau pathology; functional status of glycogen synthase kinase-3 and correlated appearance of distinct tau phospho-epitopes: neurons displaying increases in activation of phosphorylation of glycogen synthase kinase-3alpha/beta at tyrosine 279/216 also show an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. These neurons are rare in 8.5-month-old, but numerous in 18.5- and 28-month-old pR5 mice. Tau- rather than an amyloid-beta peptide-induced pathology is associated with increased neuronal tyrosine phosphorylation. Tyrosine phosphorylation only increases in neurons with fibrillar tau pathology
malfunction
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Stimulation of EphB2 attenuates tau phosphorylation through PI3K/Akt-mediated inactivation of glycogen synthase kinase-3beta
malfunction
Stimulation of EphB2 attenuates tau phosphorylation through PI3K/Akt-mediated inactivation of glycogen synthase kinase-3beta
malfunction
AMPK inhibition leads to a rapid decrease of tau phosphorylation. AMP-activated protein kinase (AMPK) is deregulated in the Alzheimer's disease brain where it co-localized with phosphorylated tau in pre-tangle and tangle bearing neurons. AMPK mice deficient for one of the catalytic alpha subunits display reduced endogenous tau phosphorylation. AMPK deficiency reduces tau pathology in the PS19 mouse model of tauopathy
malfunction
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AMPK inhibition leads to a rapid decrease of tau phosphorylation. AMP-activated protein kinase (AMPK) is deregulated in the Alzheimer's disease brain where it co-localized with phosphorylated tau in pre-tangle and tangle bearing neurons. AMPK mice deficient for one of the catalytic alpha subunits display reduced endogenous tau phosphorylation. AMPK deficiency reduces tau pathology in the PS19 mouse model of tauopathy
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malfunction
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functional status of glycogen synthase kinase-3 and correlated appearance of distinct tau phospho-epitopes: neurons displaying increases in activation of phosphorylation of glycogen synthase kinase-3alpha/beta at tyrosine 279/216 also show an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. These neurons are rare in 8.5-month-old, but numerous in 18.5- and 28-month-old pR5 mice. Tau- rather than an amyloid-beta peptide-induced pathology is associated with increased neuronal tyrosine phosphorylation. Tyrosine phosphorylation only increases in neurons with fibrillar tau pathology; functional status of glycogen synthase kinase-3 and correlated appearance of distinct tau phospho-epitopes: neurons displaying increases in activation of phosphorylation of glycogen synthase kinase-3alpha/beta at tyrosine 279/216 also show an intense rather than moderate AT8 (phospho-Ser202/Thr205 tau) immunoreactivity, and immunoreactivity for AT100 (phospho-Ser212/Thr214 tau) and phosphorylated Ser422, phospho-epitopes associated with fibrillar tau pathology. These neurons are rare in 8.5-month-old, but numerous in 18.5- and 28-month-old pR5 mice. Tau- rather than an amyloid-beta peptide-induced pathology is associated with increased neuronal tyrosine phosphorylation. Tyrosine phosphorylation only increases in neurons with fibrillar tau pathology
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malfunction
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abnormal tau phosphorylation (p-tau) occurs after hypoxic damage to the brain associated with traumatic brain injury and stroke
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physiological function
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the GSK-3beta-mediated high phosphorylation of protein tau induces synapse loss and neuronal death
physiological function
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GSK3beta regulates both tau phosphorylation and total tau levels through protein phosphatase-2A
physiological function
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GSK-3beta is a multifunctional Ser/Thr kinase that plays important roles in necrosis and apoptosis of cardiomyocytes
physiological function
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increased GSK-3 correlates with increased cell death, GSK-3 plays a very important role in L-DOPA neurotoxicity, as well as in neurodegeneration
physiological function
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cisplatin-induced cytotoxicity may be associated with modulation of GSK-3 activation
physiological function
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protein tau phosphorylation plays an essential role in adult hippocampal neurogenesis and GSK-3 facilitates neurogenesis only in the presence of tau proteins, tau hyperphosphorylation induced by activating GSK-3 promotes neurogenesis
physiological function
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mitochondrial hexokinase II is a promoter of neuronal survival under the regulation of GSK-3
physiological function
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GSK-3 is necessary and sufficient for cardiomyocyte differentiation in mesenchymal stem cells, GSK-3beta in the cytosol induces cardiomyocyte differentiation of mesenchymal stem cells through down-regulation of beta-catenin. In contrast, GSK-3alpha in the nucleus inhibits cardiomyocyte differentiation through down-regulation of c-Jun
physiological function
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glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication
physiological function
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GSK-3-regulated signal transduction pathways are important for stem cell maintenance and may be involved in events controlling cell differentiation
physiological function
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GSK3 negatively regulates mycobacteria-induced interleukin-10 production in human monocytes
physiological function
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the neuron-specific isoform GSK-3beta2 is required for axon growth by phosphorylating microtubule-associated proteins including protein tau
physiological function
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GSK-3 activity is required for tau filaments to inhibit kinesin-dependent FAT
physiological function
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GSK-3beta activation is required for memory reconsolidation in the adult brain
physiological function
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activation of GSK-3beta results in the inhibition of the Wnt signaling pathway
physiological function
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GSK-3beta is a critical mediator of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium iodide-induced neurotoxicity through its ability to regulate mitochondrial functions
physiological function
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glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase that phosphorylate protein substrates involved in Alzheimer's disease (AD), such as microtubule-associated protein tau and amyloid precursor protein (APP). Splicing variant GSK-3beta2 has lower phosphorylation activity to tau at Alzheimer disease-relevant epitope Ser396 than GSK-3b 1 in cells, whereas the two variants exhibit equivalent levels of phosphorylation activities to amyloid precursor protein. Tau is an unfavorable substrate of GSK-3beta2. Changes in the balance of GSK-3beta2/-3beta1 in neurons underlie tau hyperphosphorylation in Alzheimer's disease. The intracellular domain Thr668 of APP is phosphorylated by GSK-3beta, the phosphorylation regulates APP function and metabolism
physiological function
TTBK2 is a multifunctional kinase. TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. The TTBK2 pathway may be independent of the biogenesis of the ciliary transition zone. TTBK2 can also bind to EB1 through its SxIP motifs, where EB1 is a microtubule plus-end tracking protein required for ciliogenesis
physiological function
TTBK2 is a multifunctional kinase. TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. The TTBK2 pathway may be independent of the biogenesis of the ciliary transition zone. TTBK2 can also bind to EB1 through its SxIP motifs, where EB1 is a microtubule plus-end tracking protein required for ciliogenesis
physiological function
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role for TTBK1 in pre-tangle formation prior to the formation of fibrillar tau. Tau is phosphorylated at Ser422 at an early/intermediate stage in neurofibrillary tangle formation
physiological function
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glycogen synthase kinase-3 (GSK-3beta) and protein phosphatase 2A (PP2A) are thought to control the levels of tau phosphorylation. No alteration in the activities of GSK-3beta and PP2A during episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Tau dephosphorylation following ischaemia is not dependent on GSK-3beta or PP2A activity, but is associated with AMPK dephosphorylation
physiological function
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tau is primarily a neuronal microtubule-associated protein that has functions related to the stabilisation of microtubules. Phosphorylation of tau is usually a very rapid and reversible process, which is mediated by the opposing actions of several protein kinases and phosphatases. Tau phosphorylation is increased during embryonic development, and in neurodegenerative conditions. Phosphorylation of tau is an important dynamic and regulatory element involved in the binding of tau to tubulin, ole for GSK-3 activity on physiological tau function and on tau dysfunction in neurodegenerative disease, glycogen synthase kinase-3 activity and tau function in normal and diseased brain, detailed overview. In neurons, the primary location of tau is in axons, where it is presumed to act as a stabilising protein for the microtubule cytoskeleton. Tau has an important function in maintaining microtubule dynamic instability, through dual processes that result in the lengthening and shortening of microtubules in response to external signals. Increased tau phosphorylation leads to its detachment from tubulin, thereby, enhancing microtubule disassembly and reducing microtubule stability. Highly phosphorylated forms of tau bind less well to microtubules, resulting in a loss of the microtubule-stabilising properties of tau and ultimately the collapse of the neuronal cytoskeleton. Tau phosphorylation also influences the positioning of tau in dendrites, and the association of tau with plasma membranes and nuclei. Elevated phosphorylation results in the relocalisation of tau fromaxons into the somatodendritic region of neurons. Protein 14-3-3 recognises GSK-3 phosphorylated at Ser9, and the association of tau with this complex is believed to regulate its phosphorylation by GSK-3, since in human embryonic kidney cells, tau phosphorylation by GSK-3 is suppressed in the absence of 14-3-3, but GSK-3 is active and phosphorylates tau if 14-3-3 is present. The phosphorylation of tau by GSK-3 reduces the ability of tau to promote microtubule assembly in vitro and in cells. Priming of tau for GSK-3 phosphorylation is frequently provided by the activity of PKA, CK1, or CK2 on unphosphorylated substrates, although other kinases, such as members of the mitogen-activated protein kinase family, or cdk5, can also initiate priming on some GSK-3 substrates. GSK-3 remains a principal candidate kinase for both physiological and pathological tau phosphorylation, overview. GSK-3 in cells is important for the maintenance of healthy functional neurons, and changes in tau phosphorylation are likely be indicative of reduced neuronal viability
physiological function
glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. GSK-3 isoforms function redundantly in some settings, while, in others, they exhibit distinct activities. In the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin; in the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin. Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. GSK-3 isoforms function redundantly in some settings, while, in others, they exhibit distinct activities. In the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin
physiological function
the enzyme phosphhorylates some residues on tau associated with Alzheimer's disease; the enzyme phosphhorylates some residues on tau associated with Alzheimer's disease, phosphorylation of the microtubule associated protein tau. Inhibitor-2 phosphorylation is differentially regulated by GSK3beta1 and GSK3beta2, overview
physiological function
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the pathogenesis of Alzheimer's disease includes hyperphosphorylation of tau protein which results in the self-assembly of tangles of paired helical fragments and straight filaments. Defective tau protein causes the dementia leading to Alzheimer's disease
physiological function
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stimulation of GSK-3beta both in vitro and in vivo induces tau hyperphosphorylation with impairments of the cognitive functions, whereas inhibition of GSK-3beta improves tau pathologies and memory deficits. Activation of EphB2 receptor kinase arrests tau hyperphosphorylation through PI3K-/Akt-mediated GSK-3beta inhibition. Activation of GSK-3beta inhibits long-term potentiation and impairs synaptic function
physiological function
stimulation of GSK-3beta both in vitro and in vivo induces tau hyperphosphorylation with impairments of the cognitive functions, whereas inhibition of GSK-3beta improves tau pathologies and memory deficits. Stimulation of EphB2 upregulates PI3K and Akt with inhibition of GSK-3beta. Stimulation of EphB2 attenuates tau phosphorylation both in vitro and in hippocampus of human tau transgenic mice
physiological function
AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Endogenous AMPK activation in mouse primary neurons induces an increase of tau at multiple sites. AMPK regulates tau phosphorylation in mouse primary neurons as well as in vivo, and thus suggest that AMPK could be a key player in the development of Alzheimer's disease pathology. The two alpha subunits of AMPK can have distinct roles. AMPKalpha2, which is the most highly expressed of the catalytic subunit in the brain, is responsible for the detrimental effects observed following ischemic stroke in mice. AMPK activation increases tau phosphorylation in primary neurons and affects tau binding to microtubules. AMPK controls basal tau phosphorylation levels
physiological function
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glycogen synthase kinase-3 plays an important role in the pathogenesis of Diabetes mellitus and Alzheimer's disease. Diabetic rats display an increased GSK-3 activity, and decreased activity and expression of Akt. And Abeta40 and Abeta42 are overproduced and the microtubule-associated protein tau is hyperphosphorylated in the hippocampus. Selective inhibition of GSK-3 attenuates the conditions of Abeta overproduction and tau hyperphosphorylation. GSK-3 regulates both the production of Amyloidbeta and the phosphorylation of tau in rat brain and may therefore contribute to Diabetes mellitus caused Alzheimer disease-like neurological defects. Hyperglycemia induces strong activity of GSK-3 and lowers activity of Akt in rat brain. The production of Abeta40 and Abeta42 is increased significantly while activation of GSK-3 and inhibition of Akt are induced in Diabetes mellitus
physiological function
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AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Endogenous AMPK activation in mouse primary neurons induces an increase of tau at multiple sites. AMPK regulates tau phosphorylation in mouse primary neurons as well as in vivo, and thus suggest that AMPK could be a key player in the development of Alzheimer's disease pathology. The two alpha subunits of AMPK can have distinct roles. AMPKalpha2, which is the most highly expressed of the catalytic subunit in the brain, is responsible for the detrimental effects observed following ischemic stroke in mice. AMPK activation increases tau phosphorylation in primary neurons and affects tau binding to microtubules. AMPK controls basal tau phosphorylation levels
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physiological function
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glycogen synthase kinase-3 (GSK-3beta) and protein phosphatase 2A (PP2A) are thought to control the levels of tau phosphorylation. No alteration in the activities of GSK-3beta and PP2A during episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Tau dephosphorylation following ischaemia is not dependent on GSK-3beta or PP2A activity, but is associated with AMPK dephosphorylation
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additional information
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glycogen synthase kinase-3beta2 has lower phosphorylation activity to tau than glycogen synthase kinase-3beta1. The lower tau phosphorylation activity of GSK-3beta2 is due to the weak interaction of its C-terminal tail with tau
additional information
structure and sequence analysis of TTBK2, potential homologues of the TTBK2 noncatalytic region, detailed overview
additional information
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isozymes GSK-3alpha and GSK-3beta share many substrates and appear to be able to compensate partially for each other, although they also appear to have distinct functions
additional information
amino acids 345367 of GSK-3beta are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells; amino acids 417-430 of GSK-3alpha are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells
additional information
amino acids 345367 of GSK-3beta are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells; amino acids 417-430 of GSK-3alpha are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells
additional information
compared to GSK3beta1, the GSK3b2 isoform contains a 13 amino acid insert, which lies within the catalytic domain (between residues 303 and 304 of GSK3beta1), in a linker region flanked by a-helices (between domain X and XI)
additional information
compared to GSK3beta1, the GSK3b2 isoform contains a 13 amino acid insert, which lies within the catalytic domain (between residues 303 and 304 of GSK3beta1), in a linker region flanked by a-helices (between domain X and XI)
additional information
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homology modeling, simulation and docking studies with L-glutamic acid, memantine, tacrine, and ropinirol ligands, of Tau-protein kinase, overview
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + amyloid precursor protein
ADP + phosphorylated amyloid precursor protein
-
-
-
-
?
ATP + beta-tubulin
ADP + beta-tubulin phosphate
-
isoenzyme tau-tubulin kinase
-
-
?
ATP + cAMP response element-binding protein
ADP + phosphorylated cAMP response element-binding protein
-
-
-
-
?
ATP + coronavirus nucleocapsid protein
ADP + phosphorylated coronavirus nucleocapsid protein
-
phosphorylation sites are at Ser177, Ser181, Ser184, Ser185, Ser187, Ser189, Ser191, Ser203, and Ser207
-
-
?
ATP + DIWKKFELLPTPPLSPSRRSG
ADP + DIWKKFELLP(P)TPPL(P)SPSRRSG
-
c-Myc
-
?
ATP + EEPQTVPEMPGETPPLSPIDMESQER
ADP + EEPQTVPEMPGE(P)TPPL(P)SPIDMESQER
-
c-Jun
-
?
ATP + FITC-GSRSRTPSLP
ADP + FITC-GSRSRTP-phosphoserine-LP
-
synthetic fluorescence-labeled peptide substrate derived from residues 207-216 of tau protein, phosphorylation of S214 by SGK1
-
-
?
ATP + glycogen synthase
ADP + phosphorylated glycogen synthase
-
-
-
-
ATP + H-Arg-Arg-Arg-Ala-Ala-Glu-Glu-Leu-Asp-Ser-Arg-Ala-Gly-pSer-Pro-Gln-Leu-OH
ADP + ?
-
-
-
-
?
ATP + JHMV-N protein
ADP + phosphorylated JHMV-N protein
-
phosphorylation sites are at Ser197, Ser201, Ser-205, and Ser-209
-
-
?
ATP + KAUSSPTVSRKTD
ADP + KAUSSPTVSRKTD phosphate
-
synthetic peptide p25/F3
-
-
?
ATP + KRREILSRRPpSYR
ADP + ?
-
KRREILSRRPpSYR is selectively phosphorylated by GSK-3 and therefore acts as a competitive inhibitor of other GSK-3 substrates
-
-
?
ATP + LLNASGSTSTPAPSRTASFSESR
ADP + LLNASGSTS(P)TPAP(P)SRTASFSESR
-
ATP-citrate lyase
-
?
ATP + MADSRPKPANKTPPK
ADP + MADSRPKPANKTPPK phosphate
-
synthetic peptide F5f
-
-
?
ATP + nuclear factor-kappaB
ADP + phosphorylated nuclear factor-kappaB
-
-
-
-
?
ATP + PANKTPPKSPGEPAKDPAAK
ADP + PANKTPPKSPGEPAKDPAAK phosphate
-
synthetic peptide p25/F5a
-
-
?
ATP + phospho-glycogen synthase peptide-2
ADP + phosphorylated phospho-glycogen synthase peptide-2
-
GSK3 substrate
-
-
-
ATP + protein
ADP + phosphoprotein
-
autophosphorylation at Tyr and Ser
-
-
-
ATP + protein PHF-1 (Ser396/404)
ADP + protein PHF-1 (Ser396/404) phosphate
-
-
-
-
?
ATP + pyruvate dehydrogenase
ADP + pyruvate dehydrogenase phosphate
-
PDH is phosphorylated and inactivated in vitro and also in betaA-treated hippocampal cultures, resulting in mitochondrial dysfunction which will contribute to neuronal death
-
-
?
ATP + RRREEETEEE
ADP + RRREEETEEE phosphate
-
synthetic peptide CKII substrate
-
-
?
ATP + RSRSRSRSRSRSPPPVSK
ADP + phosphorylated RSRSRSRSRSRSPPPVSK
-
SC35-derived peptide 180-197, recombinant GSK-3beta
-
-
?
ATP + [amyloid precursor protein]
ADP + O-phospho-[amyloid precursor protein]
-
phosphorylation of the intracellular domain Thr668 of APP by GSK-3beta
-
-
?
ATP + [FRAT-2 protein]
ADP + phosphorylated [FRAT-2 protein]
-
i.e. frequently rearranged in advanced T-cell lymphoma protein 2, phosphorylation by GSK3beta
-
-
?
protein tau + ATP
phosphorylated protein tau + ADP
-
the microtubule-associated protein tau is the principal component of the paired helical filaments - PHFs - found in the brains of patients with Alzheimer disease, and PHF-tau is hyperphosphorylated
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
-
-
-
?
ATP + beta-catenin
ADP + phosphorylated beta-catenin
-
substrate of isoform GSK-3beta
-
-
?
ATP + mammalian histone H1
ADP + phosphorylated mammalian histone H1
-
-
-
-
?
ATP + mammalian histone H1
ADP + phosphorylated mammalian histone H1
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylates tau and forms paired helical filament epitopes, tau/K1, K2, K3 and tau/4 repeat
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylates tau on S202, T231, S396, and S400 but not on S262, S235, and S404. Phosphorylates tau directly at S202 but requires the previous phosphorylation on S235 to phosphorylate T231, once a priming kinase phosphorylates S404, GSK3beta sequentially phosphorylates S400 and then S396
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
GSK-3beta-mediated hyperphosphorylated forms of tau are degradable by the proteasomal machinery
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
-
691083, 702438, 702637, 702646, 703599, 704555, 705246, 705263, 705280, 705440, 705916, 706016, 706672
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
enzyme can also phosphorylate bovine tau
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylates tau protein into Alzheimer disease-like forms, resulting in neuronal death
-
?
ATP + protein tau
ADP + protein tau phosphate
-
when a beta-mediated aggregated tau is used as a substrate for TPKII, an 8fold increase in the rate of TPKII-mediated tau phosphorylation is observed
-
?
ATP + protein tau
ADP + protein tau phosphate
-
6 isoforms of human tau expressed in adult human brain
-
?
ATP + protein tau
ADP + protein tau phosphate
-
prior phosphorylation of tau by isoenzyme TPKII strongly enhances the action of TPKI
-
?
ATP + protein tau
ADP + protein tau phosphate
-
regulates PDH and participates in energy metabolism and acetylcholine synthesis
-
?
ATP + protein tau
ADP + protein tau phosphate
-
direct tau phosphorylation by TTBK1 at Ser198, Ser199, Ser202 and Ser422
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
TTBK2 (1-331) phosphorylates residues Ser208 and Ser210
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
in vitro, GSK-3beta phosphorylates protein tau at 14 sites, all tau protein isoforms are phosphorylated by GSK-3beta which changes filament polymerization levels and filament morphology
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
-
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
role of GSK3 as a key mediator of tau hyperphosphorylation, whereas Cdk5 acts as a modulator of tau hyperphosphorylation via the inhibitory regulation of GSK3
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
T231 is the primary phosphorylation site for GSK3beta, the tau227-237 (AVVRTPPKSPS) derived from tau containing T231P232 motif is the GSK3beta binding site with high affinity (Kd = 0.00082 mmol/L), tau mutant T231A completely abolishes tau phosphorylation by GSK3beta
-
-
?
ATP + protein tau
ADP + protein tau phosphate
the antagonist of GSK-3beta in protein tau phosphorylation is the phosphatase PP2A
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylation occurs at Ser-396/Ser-404
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
PKA transfers about 2 mol of phosphate per mole of the shortest protein tau isoform and phosphorylates Ser156, 235, 267, 320 and 327 (corresponding to Ser214, 324, 356, 409 and 416 of the longest protein tau isoform)
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylation at Ser9
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
protein tau primed by CK1 functions as an effective phosphate acceptor for GSK-3beta
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
-
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
microtubule-associated protein, enzyme can also phosphorylate human tau
-
?
ATP + protein tau
ADP + protein tau phosphate
-
microtubule-associated protein
-
?
ATP + protein tau
ADP + protein tau phosphate
-
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors, recombinant GSK-3beta
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
tau in Alzheimer disease brain is highly phosphorylated and aggregates into paired helical filaments comprising characteristic neurofibrillary tangles, overview
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
determination of several phosphorylation sites, e.g. Ser258, Ser289, Ser262, and Ser356 within the microtubule-binding repeats or at Ser184 and Ser185 of the central region, for casein kinase I, casein kinase 2, and glycogen synthase kinase-3beta in insoluble tau, PHF-tau, extracted from Alzheimer brain and of tau from control healthy brain by mass spectrometry, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 associated with p25
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau, especially at the primed epitope T231 negatively regulates tau-microtubule interactions, different effects of phosphorylation on primed T231 and unprimed S396/S404 epitopes of tau, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
protein 14-3-3 mediates phosphorylation of microtubule-associated protein tau by serum- and glucocorticoid-induced protein kinase 1 SGK1, which forms an activated ternary complex with protein 14-3-3theta
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is primarily found in neurons, regulation of tau phosphorylation by GSK3beta via interaction with FRAT-1 and FRAT-2, i.e. frequently rearranged in advanced T-cell lymphoma proteins
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation by GSK-3beta is involved in development of neurodegenerative Alzheimer's disease, the tau phosphorylation activity by GSK-3beta is further increased by soluble toxic beta-amyloid oligomers, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 associated with p25, recombinant bacterially expressed human tau protein as substrate, phosphorylation of the AT8 and AT180 epitopes, and at T231 of the Alzheimer's mitotic epitope TG-3
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation at the C-terminus, lower activity with C-terminally truncated tau D421 compared to the wild-type tau, the truncated tau protein forms sarcosyl-insoluble aggregates
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of primed and unprimed sites by GSK3beta, wild-type and recombinant tau, recombinant GSK3beta S9A
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of S214 by SGK1, recombinant tau S214A is no substrate
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
phoshorylation at residues Ser404, Ser199, Ser202 and Thr231
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
phosphorylation at Ser208 and Ser210
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau isoforms in the human central nervous system and GSK-3 phosphorylation sites. Isozymes GSK-3alpha and GSK-3beta1/2 differentially phosphorylate tau, e.g. Ser396 in tau is phosphorylated by both splice variants, whereas Ser199 is a significant target of GSK-3beta1, but not of GSK-3beta2 activity
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
phosphorylation at Ser422, no phosporylation at Ser231
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation level of tau at Thr205, Thr231, Ser396 and tau-1 sites
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
the enzyme is a serine/threonine protein kinase
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
the enzyme phosphorylates in tau residues S46, T50, S69, and T71 at the N-terminus, residues T149, T153, T175, T181, S184, S195, S198, S199, S202, T205, S210, T212, S214, T217, T220, T231, S235, S237, S241, and T245 in the central, proline-rich domain, residues S258 and S262 in the repeat domain R1 domain, residues S285, S289, and S324 in the repeat domain R2 domain, and residues S352, S356, T373, S396, S400, S404, S409, and S413 in the repeat domain R4 domain, there are no phosphorylation sites of GSK-3 in the repeat domain R3 domain, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
activity in organisms with mutated APP and tau, not in wild-type, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 substrate in brain, cdk5 associated with p39, tau is a microtubule-associated and developmentally regulated protein involved in axonal development in neurons, tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
hyperphosphorylation of tau by CDK5 is involved in apoptosis and neurodegeneration in Alzheimer's disease, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation by GSK-3beta is involved in development of neurodegenerative Alzheimer's disease, the tau phosphorylation activity by GSK-3beta is further increased by soluble toxic beta-amyloid oligomers, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation in vivo is stimulated by extracellular signal-regulated kinase Erk phosphorylation and apolipoprotein isozyme E4, to a lesser extent by isozyme apoE3, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of the PHF-1 epitope at Ser396 and Ser404 by CDK5
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
preferred substrate of cdk5 associated with p39, recombinant bacterially expressed human tau protein as substrate, phosphorylation at Ser202 and Thr205
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
recombinant human tau protein expressed in transgenic mice
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
AMPK phosphorylate tau in vitro at several epitopes including Thr231, Ser262/356, Ser396, Ser409 and Ser422, whereas Ser199, Ser202, Ser235, Ser400, and Ser404 are not phosphorylated by AMPK
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
phosphorylation level of tau at Thr205, Thr231, Ser396 and tau-1 sites
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
AMPK phosphorylate tau in vitro at several epitopes including Thr231, Ser262/356, Ser396, Ser409 and Ser422, whereas Ser199, Ser202, Ser235, Ser400, and Ser404 are not phosphorylated by AMPK
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
abnormal hyperphosphorylation of tau by PKA and GSK-3 is associated with Alzheimer's disease and other tauopaties leading to neuronal degeneration
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is microtubule-associated, phopshorylation at T231 by CDK5 causes its release into the cytoplasm
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation at T231, no activity with tau mutant T231A
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation by PKA at Ser214, and by GSK-3 at Ser404, Ser396, Ser198, Ser199, and Ser202
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau at various sites
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation at Ser198, Ser199, Ser202, Ser396, and Ser404
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation at GSK-3beta sensitive but AMPK insensitive residues Ser202/Thr205
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
tau phosphorylation at GSK-3beta sensitive but AMPK insensitive residues Ser202/Thr205
-
-
?
glycogen synthase + ATP
phosphorylated glycogen synthase + ADP
-
proline-directed kinase
-
-
?
glycogen synthase + ATP
phosphorylated glycogen synthase + ADP
-
-
-
?
glycogen synthase + ATP
phosphorylated glycogen synthase + ADP
-
-
-
-
?
additional information
?
-
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
-
TPKI cannot phosphorylate K1, K2 and K3 peptides, histones H1, H2A, H2B and H3 and beta casein
-
-
-
additional information
?
-
-
novel isoenzyme, distinct from TPKI, TPKII CKI and CKII, no activity toward beta-casein and neurofilament, no reaction with synthetic peptides F5a PANKTPPKSPGEPAKDPAAK, F5n MADSRPK, F5d MADSRKPAN, F5e MADSRPAE and 8656 RKRARKE, only weak activity with histones H1, H2a and H2b as substrates
-
-
-
additional information
?
-
-
glycogen synthase kinase-3beta also performs serine/threonine protein kinase reaction, EC 2.7.11.1, with other substrates than tau, e.g. it phosphorylates the glycogen synthase
-
-
-
additional information
?
-
enzyme regulates cell fate in Dictyostelium
-
-
-
additional information
?
-
-
possible role of the sgg protein in a signal transduction pathway necessary for intercellular communication at different stages of development
-
-
-
additional information
?
-
-
enzyme acts as a repressor of engrailed autoregulation
-
-
-
additional information
?
-
-
implicated in cell-fate determination and differentiation, phosphorylates several regulatory proteins that are activated by dephosphorylation in response to hormones or growth factors
-
-
-
additional information
?
-
-
enzyme of the lithium-sensitive wnt signaling pathway
-
-
-
additional information
?
-
-
enzyme forms part of the wingless signalling pathway. GSK-3beta activity is negatively regulated by phosphorylation on serine 9 and positively regulated by phosphorylation on tyrosine 216. Enzyme may also be regulated at the transcriptional level
-
-
-
additional information
?
-
-
abnormal phosphorylation of tau in dividing cells leads to its accumulation in the cytosol as microtubule-free form, Cdk5 is involved in neurodegenerative mechanisms
-
-
-
additional information
?
-
-
GSK-3 affects the tau-mRNA splicing of exon 10 via phosphorylation of the splicing factors of the serine/arginine-rich splicing factor SR family, e.g. SC35, leading to priming and dislocation of the splicing factor, aberrant tau splicing contributes to tauopathies including Alzheimer's disease, overview
-
-
-
additional information
?
-
-
GSK3beta and PKA work coordinatedly on tau phosphorylation
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of organisms with Alzheimer's disease leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of patients suffering from Alzheimer's disease leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
phosphorylated tau is important in cytoskeleton assembly
-
-
-
additional information
?
-
-
protein 14-3-3 facilitates tau phosphorylation by SGK1 and regulates its subcellular localization in the nucleus or cytoplasm, overview
-
-
-
additional information
?
-
-
the enzyme participates in Alzheimer's disease
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation in brain, but phosphorylation of glycogen synthase and other proteins, EC 2.7.11.1, in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation in brain, but phosphorylation of glycogen synthase and other proteins, EC 2.7.11.1, in different tissues
-
-
-
additional information
?
-
-
GSK3beta catalyzes tau phosphorylation in brain, but phosphorylation of glycogen synthase and other proteins, EC 2.7.11.1, in different tissues
-
-
-
additional information
?
-
-
GSK3beta, EC 2.7.11.1, and PKA, EC 2.7.11.11, catalyze tau phosphorylation in brain, but phosphorylation of glycogen synthase and other proteins in different tissues
-
-
-
additional information
?
-
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview
-
-
-
additional information
?
-
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview
-
-
-
additional information
?
-
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview
-
-
-
additional information
?
-
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview
-
-
-
additional information
?
-
in addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein
-
-
-
additional information
?
-
-
development and evaluation of a capillary electrophoresis-based method for in vitro determination of protein tau phosphorylation by GSK3beta. When the GSK3beta-dependent phosphorylation reaction is carried out in the presence of heparin or heparan sulfate, an increase in the maximum phosphorylation levels is clearly observed, suggesting the appearance of new phosphorylatable sites on protein tau generated by the presence of sulfated polysaccharides
-
-
-
additional information
?
-
GSK-3alpha-specific requirement for priming of tau protein
-
-
-
additional information
?
-
GSK-3alpha-specific requirement for priming of tau protein
-
-
-
additional information
?
-
-
recombinant splicing variant GSK-3beta2 has lower phosphorylation activity to tau than splicing variant GSK-3beta1 in vitro, although the phosphorylation activities of the two variants to a synthetic peptide substrate pGS-2 are comparable
-
-
-
additional information
?
-
-
tau possesses 80 phosphorylatable serine and threonine residues
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of mutants leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of mutants leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
rapid, reversible cold-water stress-induced hyperphosphorylation of tau S199, S202, T205, T231, and S235 in hippocampal and cerebral region of the brain, hyperphosphorylation of tau is associated to the Alzheimer's disease
-
-
-
additional information
?
-
-
cdk5 also performs the kinase reaction of EC 2.7.11.22
-
-
-
additional information
?
-
enzyme is involved in the cellular response to insulin, the enzyme is highly phosphorylated on tyrosine and thus active in resting cells
-
-
-
additional information
?
-
-
implicated in the hormonal control of several regulatory proteins including glycogen synthase and the transcription factor c-jun
-
-
-
additional information
?
-
-
activation and deregulation of GSK-3, e.g. by wortmannin or GF-109203X, induces Alzheimer-like tau hyperphosphorylation in hippocampus, the hyperphosphorylated tau forms neurofibrillary tangle
-
-
-
additional information
?
-
-
CDK5-dependent clustering of endoplasmic reticulum ER and mitochondria during ceramide-mediated neuronal death: neurotoxic calcium transfer from ER to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau, inhibition of the process leads to cell death
-
-
-
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
-
additional information
?
-
-
does not phosphorylate tau at epitope Ser 262
-
-
-
additional information
?
-
-
MDS1 is not essential during normal vegetative growth but appears to be required for meiosis
-
-
-
additional information
?
-
enzyme is involved in the induction of meiosis
-
-
-
additional information
?
-
-
MCK1 encodes a positive regulator of meiosis and spore formation. MCK1 is required in vegetative cells for basal IME1 expression, it is also required for efficient ascus maturation. MCK1 plays a role in governing centromere function during vegetative growth as well as sporulation
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + amyloid precursor protein
ADP + phosphorylated amyloid precursor protein
-
-
-
-
?
ATP + nuclear factor-kappaB
ADP + phosphorylated nuclear factor-kappaB
-
-
-
-
?
ATP + SC35
ADP + phosphorylated SC35
-
substrate prephosphorylated SC35, SC35 is a member of the SR family of serine/arginine-rich splicing factors
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
tau in Alzheimer disease brain is highly phosphorylated and aggregates into paired helical filaments comprising characteristic neurofibrillary tangles, overview
-
-
?
ATP + [amyloid precursor protein]
ADP + O-phospho-[amyloid precursor protein]
-
phosphorylation of the intracellular domain Thr668 of APP by GSK-3beta
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
phosphorylates tau on S202, T231, S396, and S400 but not on S262, S235, and S404. Phosphorylates tau directly at S202 but requires the previous phosphorylation on S235 to phosphorylate T231, once a priming kinase phosphorylates S404, GSK3beta sequentially phosphorylates S400 and then S396
-
-
?
ATP + protein tau
ADP + protein tau phosphate
-
prior phosphorylation of tau by isoenzyme TPKII strongly enhances the action of TPKI
-
?
ATP + protein tau
ADP + protein tau phosphate
-
regulates PDH and participates in energy metabolism and acetylcholine synthesis
-
?
ATP + protein tau
ADP + protein tau phosphate
-
microtubule-associated protein
-
?
ATP + protein tau
ADP + protein tau phosphate
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 associated with p25
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau, especially at the primed epitope T231 negatively regulates tau-microtubule interactions, different effects of phosphorylation on primed T231 and unprimed S396/S404 epitopes of tau, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
protein 14-3-3 mediates phosphorylation of microtubule-associated protein tau by serum- and glucocorticoid-induced protein kinase 1 SGK1, which forms an activated ternary complex with protein 14-3-3theta
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is primarily found in neurons, regulation of tau phosphorylation by GSK3beta via interaction with FRAT-1 and FRAT-2, i.e. frequently rearranged in advanced T-cell lymphoma proteins
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation by GSK-3beta is involved in development of neurodegenerative Alzheimer's disease, the tau phosphorylation activity by GSK-3beta is further increased by soluble toxic beta-amyloid oligomers, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
P49840, P49841
phoshorylation at residues Ser404, Ser199, Ser202 and Thr231
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
Q6IQ55
phosphorylation at Ser208 and Ser210
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau isoforms in the human central nervous system and GSK-3 phosphorylation sites. Isozymes GSK-3alpha and GSK-3beta1/2 differentially phosphorylate tau, e.g. Ser396 in tau is phosphorylated by both splice variants, whereas Ser199 is a significant target of GSK-3beta1, but not of GSK-3beta2 activity
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
activity in organisms with mutated APP and tau, not in wild-type, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 substrate in brain, cdk5 associated with p39, tau is a microtubule-associated and developmentally regulated protein involved in axonal development in neurons, tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
hyperphosphorylation of tau by CDK5 is involved in apoptosis and neurodegeneration in Alzheimer's disease, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation by GSK-3beta is involved in development of neurodegenerative Alzheimer's disease, the tau phosphorylation activity by GSK-3beta is further increased by soluble toxic beta-amyloid oligomers, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau phosphorylation in vivo is stimulated by extracellular signal-regulated kinase Erk phosphorylation and apolipoprotein isozyme E4, to a lesser extent by isozyme apoE3, overview
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
Q5EG47
AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
Q9WV60
recombinant human tau protein expressed in transgenic mice
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
Q5EG47
AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
abnormal hyperphosphorylation of tau by PKA and GSK-3 is associated with Alzheimer's disease and other tauopaties leading to neuronal degeneration
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is microtubule-associated, phopshorylation at T231 by CDK5 causes its release into the cytoplasm
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation of tau at various sites
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
P18266
-
-
-
?
additional information
?
-
Q39010
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
Q39012
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
Q39019
AtK-1 kinase is involved in reproduction-specific processes
-
-
-
additional information
?
-
-
glycogen synthase kinase-3beta also performs serine/threonine protein kinase reaction, EC 2.7.11.1, with other substrates than tau, e.g. it phosphorylates the glycogen synthase
-
-
-
additional information
?
-
P51136
enzyme regulates cell fate in Dictyostelium
-
-
-
additional information
?
-
-
possible role of the sgg protein in a signal transduction pathway necessary for intercellular communication at different stages of development
-
-
-
additional information
?
-
-
enzyme acts as a repressor of engrailed autoregulation
-
-
-
additional information
?
-
-
implicated in cell-fate determination and differentiation, phosphorylates several regulatory proteins that are activated by dephosphorylation in response to hormones or growth factors
-
-
-
additional information
?
-
-
enzyme of the lithium-sensitive wnt signaling pathway
-
-
-
additional information
?
-
-
enzyme forms part of the wingless signalling pathway. GSK-3beta activity is negatively regulated by phosphorylation on serine 9 and positively regulated by phosphorylation on tyrosine 216. Enzyme may also be regulated at the transcriptional level
-
-
-
additional information
?
-
-
abnormal phosphorylation of tau in dividing cells leads to its accumulation in the cytosol as microtubule-free form, Cdk5 is involved in neurodegenerative mechanisms
-
-
-
additional information
?
-
-
GSK-3 affects the tau-mRNA splicing of exon 10 via phosphorylation of the splicing factors of the serine/arginine-rich splicing factor SR family, e.g. SC35, leading to priming and dislocation of the splicing factor, aberrant tau splicing contributes to tauopathies including Alzheimer's disease, overview
-
-
-
additional information
?
-
-
GSK3beta and PKA work coordinatedly on tau phosphorylation
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of organisms with Alzheimer's disease leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of patients suffering from Alzheimer's disease leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
phosphorylated tau is important in cytoskeleton assembly
-
-
-
additional information
?
-
-
protein 14-3-3 facilitates tau phosphorylation by SGK1 and regulates its subcellular localization in the nucleus or cytoplasm, overview
-
-
-
additional information
?
-
-
the enzyme participates in Alzheimer's disease
-
-
-
additional information
?
-
P49840
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview
-
-
-
additional information
?
-
P49841
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview
-
-
-
additional information
?
-
P49840
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview
-
-
-
additional information
?
-
P49841
glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview
-
-
-
additional information
?
-
Q6IQ55
in addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein
-
-
-
additional information
?
-
-
naturally occurring V717I mutation of the amyloid precursor protein APP in a CT100 fragment of mutants leads to augmented age-dependent tau phosphorylation, followed by increased activation status of mitogen-activated protein kinase family members, e.g. ERK1/2, p38, and c-Jun NH2-terminal kinase, compared to the wild-type organism, naturally occurring V337M mutation of tau protein of mutants leads to age-dependent memory deficits
-
-
-
additional information
?
-
-
rapid, reversible cold-water stress-induced hyperphosphorylation of tau S199, S202, T205, T231, and S235 in hippocampal and cerebral region of the brain, hyperphosphorylation of tau is associated to the Alzheimer's disease
-
-
-
additional information
?
-
P18266
enzyme is involved in the cellular response to insulin, the enzyme is highly phosphorylated on tyrosine and thus active in resting cells
-
-
-
additional information
?
-
-
implicated in the hormonal control of several regulatory proteins including glycogen synthase and the transcription factor c-jun
-
-
-
additional information
?
-
-
activation and deregulation of GSK-3, e.g. by wortmannin or GF-109203X, induces Alzheimer-like tau hyperphosphorylation in hippocampus, the hyperphosphorylated tau forms neurofibrillary tangle
-
-
-
additional information
?
-
-
CDK5-dependent clustering of endoplasmic reticulum ER and mitochondria during ceramide-mediated neuronal death: neurotoxic calcium transfer from ER to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau, inhibition of the process leads to cell death
-
-
-
additional information
?
-
-
tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain, inhibition of tau hyperphosphorylation inhibits an associated loss in spatial memory
-
-
-
additional information
?
-
-
MDS1 is not essential during normal vegetative growth but appears to be required for meiosis
-
-
-
additional information
?
-
P21965
enzyme is involved in the induction of meiosis
-
-
-
additional information
?
-
-
MCK1 encodes a positive regulator of meiosis and spore formation. MCK1 is required in vegetative cells for basal IME1 expression, it is also required for efficient ascus maturation. MCK1 plays a role in governing centromere function during vegetative growth as well as sporulation
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
; the ATP binding site of GSK3beta sits in the hydrophobic pocket between the two lobes, enclosed by a glycine rich loop (residues 60-70) and a hinge region (residues 134-139) while the substrate binding domain is within the C-terminal region
ATP
-
-
662134, 662152, 662261, 662313, 662388, 662674, 662690, 662855, 662870, 674847, 691083, 701940, 702438, 702587, 702637, 702646, 703016, 703599, 704555, 704616, 704796, 704992, 705246, 705263, 705280, 705325, 705326, 705328, 705440, 705796, 705824, 705916, 706016, 706672, 739843, 739962, 740125, 740135, 740244, 740423, 740530, 740531, 741395, 741409
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Zn2+
-
high zinc concentrations (0.1-0.5 mM) increase glycogen synthase kinase-3beta phosphorylation on tyrosine 216, a phosphorylation associated with increased activity of this tau kinase, whereas the phosphorylation of GSK-3alpha at Y279 and the level of total GSK-3beta are not affected
additional information
Mg2+
-
-
Mg2+
-
required
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(4-amino-2-((4-chlorophenyl)amino)thiazol-5-yl)(3-nitrophenyl)methanone
-
enzyme binding structure analysis
(Rp)-adenosine 3',5'-cyclic monophosphorothionate triethyl ammonium salt
-
inhibitor of PKA
1-(4-methoxyphenyl)-6-(5-[[3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
-
1-(4-methoxyphenyl)-6-(5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
-
1-(cyclopropylmethyl)-3-[4-(5,6-difluoro-1-benzofuran-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-5-carbonitrile
-
-
1-methyl-6-(5-[[3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
-
2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole
-
-
2-(1-benzofuran-5-yl)-5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[(3-fluorobenzyl)sulfanyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[(4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[2-(3-fluorophenyl)ethyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[[(3-fluorophenyl)sulfanyl]methyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[[3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazole
-
-
2-(2,3-dihydro-1-benzofuran-5-yl)-5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazole
-
-
2-(3-ethylpiperazin-1-yl)-N-[6-(3-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]acetamide
-
-
2-chloro-5-[(2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrol-3-yl)amino]benzoic acid
-
-
2-chloro-5-[[4-(2-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-chloro-5-[[4-(2-nitrophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-chloro-5-[[4-(3-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-chloro-5-[[4-(3-methoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-chloro-5-[[4-(3-nitrophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-chloro-5-[[4-(4-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
2-[(2-chlorobenzyl)sulfanyl]-5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazole
-
-
2-[(3-chloro-4-methoxybenzyl)sulfanyl]-5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazole
-
-
2-[(3-chlorobenzyl)sulfanyl]-5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazole
-
-
2-[(4-chlorobenzyl)sulfanyl]-5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazole
-
-
2-[3-(4-methoxyphenyl)-1-benzofuran-5-yl]-5-[[3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazole
-
-
2-[3-(4-methoxyphenyl)-1-benzofuran-5-yl]-5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazole
-
-
3-(1-(2-(1H-imidazol-1-yl)ethyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(2-morpholinoethyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-1-phenyl-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(piperidin-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-(piperidin-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-hydroxypropyl)-1H-indol-3-yl)-4-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-hydroxypropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-1,2,4-triazol-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(4-(1H-imidazol-1-yl)butyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-(4-morpholinobutyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(1-methyl-7-phenoxy-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(5-bromo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(5-cyclopropyl-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(5-fluoro-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(5-iodo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(6-chloro-5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(6-hydroxy-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(6-iodo-5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-(7-hydroxy-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[1-(3-hydroxypropyl)-5-phenoxy-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[1-methyl-5-(morpholin-4-yl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[5-bromo-1-(3-hydroxypropyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[6-(benzyloxy)-1-methyl-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[7-(hydroxymethyl)-1-methyl-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-benzofuran-3-yl)-4-[7-(methoxymethyl)-1-methyl-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-4-(1-(2-morpholinoethyl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-4-(1-(3-morpholinopropyl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(1H-imidazol-1-yl)-4-(1-(3-morpholinopropyl)-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(2-chlorophenyl)-4-[(3,5-dichloro-4-hydroxyphenyl)amino]-1H-pyrrole-2,5-dione
-
-
3-(2-methoxyphenyl)-4-[[4-(methylsulfanyl)phenyl]amino]-1H-pyrrole-2,5-dione
-
-
3-(3-chlorophenyl)-4-[(3,5-dichloro-4-hydroxyphenyl)amino]-1H-pyrrole-2,5-dione
-
-
3-(3-methoxyphenyl)-4-[[4-(methylsulfanyl)phenyl]amino]-1H-pyrrole-2,5-dione
-
-
3-(4-chlorophenyl)-4-[(3,5-dichloro-4-hydroxyphenyl)amino]-1H-pyrrole-2,5-dione
-
-
3-(4-methoxyphenyl)-4-[[4-(methylsulfanyl)phenyl]amino]-1H-pyrrole-2,5-dione
-
-
3-(5,6-difluoro-1-benzofuran-3-yl)-4-(1-methyl-1H-benzo[g]indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5,7-dibromo-1-methyl-1H-indol-3-yl)-4-(7-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-benzofuran-3-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-methyl-1H-indol-3-yl)-4-(7-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-methyl-1H-indol-3-yl)-4-[6-(4-methoxyphenoxy)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-methyl-1H-indol-3-yl)-4-[6-(hydroxymethyl)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-methyl-1H-indol-3-yl)-4-[6-(prop-2-en-1-yloxy)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-bromo-1-methyl-1H-indol-3-yl)-4-[6-(prop-2-yn-1-yloxy)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-chloro-1-methyl-1H-indol-3-yl)-4-(5-fluoro-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-1-benzofuran-3-yl)-4-(5-iodo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-1-benzofuran-3-yl)-4-(6-hydroxy-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-1-methyl-1H-indol-3-yl)-4-(6-hydroxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-1-methyl-1H-indol-3-yl)-4-[6-(hydroxymethyl)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-1-methyl-1H-indol-3-yl)-4-[6-(methoxymethyl)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(5-fluoro-6-iodo-1-methyl-1H-indol-3-yl)-4-(7-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-methoxy-1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-methoxy-1-(3-(dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(5-methoxy-1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(5H-[1,3]dioxolo[4,5-f]indol-7-yl)-4-(5-fluoro-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-bromo-1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-bromo-1-(3-(dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-bromo-1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-4-(6-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-4-(7-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-4-[6-(cyclobutylmethoxy)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-4-[6-(cyclopropylmethoxy)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(6-chloro-5-fluoro-1-methyl-1H-indol-3-yl)-4-[6-(hydroxymethyl)-1-benzofuran-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(6-fluoro-1-(3-(1H-imidazol-1-yl)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-fluoro-1-(3-(dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-pyrrolo[3,2-b]pyridin-1-yl)-1H-pyrrole-2,5-dione
-
-
3-(6-fluoro-1-(3-morpholinopropyl)-1H-indol-3-yl)-4-(1Hpyrrol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(7-methoxy-1-benzofuran-3-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
-
-
3-(7-methoxy-1-benzofuran-3-yl)-4-[1-methyl-6-(trifluoromethyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-(imidazo[1,2-a]pyridin-3-yl)-4-[2-(morpholine-4-carbonyl)-1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl]-1H-pyrrole-2,5-dione
-
an imidazo[1,2-a]pyridinylindolylmaleimide
3-([[5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazol-2-yl]sulfanyl]methyl)benzo-nitrile
-
-
3-benzyl-N-[5-bromo-6-(furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrrolidine-1-carboxamide
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(2-methoxyphenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(3-methoxyphenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(3-nitrophenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(4-methoxyphenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3,5-dichloro-4-hydroxyphenyl)amino]-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione
-
-
3-[(3-chloro-4-hydroxyphenyl)amino]-4-(2-methoxyphenyl)-1H-pyrrole-2,5-dione
-
-
3-[([5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazol-2-yl]sulfanyl)methyl]benzonitrile
-
-
3-[([5-[3-(4-methoxyphenyl)-1-benzofuran-5-yl]-1,3,4-oxadiazol-2-yl]sulfanyl)methyl]benzonitrile
-
-
3-[1H-indol-3-yl]-4-[2-[4-methylpiperazin-1-yl]quinazolin-4-yl]-1H-pyrrole-2,5-dione
-
enzyme binding structure analysis
3-[4-(6-ethyl-1-benzofuran-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1-methyl-1H-indole-5-carbonitrile
-
-
3-[5-(cyclopropylethynyl)-1-methyl-1H-indol-3-yl]-4-(5-fluoro-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-[6-(4-chlorophenyl)-5-fluoro-1-methyl-1H-indol-3-yl]-4-(7-methoxy-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-[6-(benzyloxy)-1-methyl-1H-indol-3-yl]-4-(5-fluoro-1-benzofuran-3-yl)-1H-pyrrole-2,5-dione
-
-
3-[6-(hydroxymethyl)-1-benzofuran-3-yl]-4-[7-(hydroxymethyl)-1-methyl-1H-indol-3-yl]-1H-pyrrole-2,5-dione
-
-
3-[[4-(2-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3-[[4-(3-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3-[[4-(3-methoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3-[[4-(3-nitrophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3-[[4-(4-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3-[[4-(4-methoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]amino]benzoic acid
-
-
3alpha,5alpha-tetrahydroprogesterone
-
decreases only expression of GSK-3 beta in the cerebellum but not in the hypothalamus
4-[1-cyclohexyl-4-[4-fluorophenyl]-1H-imidazol-5-yl]pyrimidin-2-amine
-
enzyme binding structure analysis
4-{(2R)-2-[(1R,3R,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl}piperidine-2,6-dione
-
-
5-(2,3-dihydro-1-benzofuran-5-yl)-N-(3-fluorobenzyl)-1,3,4-oxadiazol-2-amine
-
-
5-(5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-indazole
-
-
5-([ [5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazol-2-yl]sulfanyl]methyl)-2-methoxybenzonitrile
-
-
5-[2-phenylpyrazolo[1,5-a]pyridin-3-yl]-1h-pyrazolo[3,4-c]pyridazin-3-amine
-
enzyme binding structure analysis
5alpha-dihydroprogesterone
-
decreases only expression of GSK-3 beta in the cerebellum but not in the hypothalamus
6-(5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1,3-benzothiazole
-
-
6-(5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridine
-
-
6-(5-[[4-methoxy-3-(trifluoromethyl)benzyl]sulfanyl]-1,3,4-oxadiazol-2-yl)quinoline
-
-
A-582941
-
attenuates beta-amyloid peptide 1-42-induced activation of GSK-3beta
alpha-bungarotoxin
-
attenuates beta-amyloid peptide 1-42-induced activation of GSK-3beta
caffeic acid
-
0.02 mg/ml caffeic acid decreases the activating phosphorylation of GSK-3beta
CHIR98023
-
attenuates beta-amyloid peptide 1-42-induced activation of GSK-3beta
dantrolene
-
in the presence of dantrolene, GSK-3beta activation and tau phosphorylation are decreased
enzastaurin
-
activation-related phosphorylation of Y216/Y276 is dramatically decreased following exposure to enzastaurin whereas the inhibitory phosphorylation of S21 is significantly up-regulated in glioma cells. GSK3 inhibition results in glioma cell death and reduced tumorigenicity
Insulin
-
insulin induces phosphorylation of the Ser9 residue, thereby inactivating GSK-3beta
-
KRM-189
-
74% inhibition at 0.01 mM, competes with ATP for GSK-3beta, leading to decreased Vmax and constant Km with increasing concentrations of ATP
KRM-191
-
84% inhibition at 0.01 mM, competes with ATP for GSK-3beta, leading to decreased Vmax and constant Km with increasing concentrations of ATP
methyl 3-([[5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazol-2-yl]sulfanyl]methyl)benzoate
-
-
methyllycaconitine
-
attenuates beta-amyloid peptide 1-42-induced activation of GSK-3beta
N-(5-bromo-6-phenyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-4-methylpiperidine-1-carboxamide
-
-
N-[3-cyano-6-[3-[1-piperidinyl]propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]1-naphthalenecarboxamide
-
enzyme binding structure analysis
N-[4-[3-(4-ethylpiperazin-1-yl)propyl]-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[4-[3-(dimethylamino)propyl]-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[4-[3-(morpholin-4-yl)propyl]-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[4-[ethyl(piperidin-1-ylmethyl)amino]-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[4-[methyl(piperidin-1-yl)amino]-5-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]butanamide
-
-
N-[5-(6,6-difluorocyclohexa-1,3-dien-1-yl)-4-[3-(dimethylamino)propyl]-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[5-bromo-6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-(4-ethylpiperazin-1-yl)butanamide
-
-
N-[5-bromo-6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-methylpiperidine-1-carboxamide
-
-
N-[5-bromo-6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[5-bromo-6-(furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[5-bromo-6-(tetrahydrothiophen-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[5-bromo-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-2-(4-methylpiperidin-1-yl)acetamide
-
-
N-[5-bromo-6-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[5-chloro-6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[5-phenyl-4-[3-(pyrrolidin-1-yl)propyl]-1H-pyrazolo[3,4-c]pyridazin-3-yl]butanamide
-
-
N-[6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(2-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(3-bromo-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(3-chloro-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(3-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-
N-[6-(3-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
-
-