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Information on EC 2.7.11.26 - tau-protein kinase
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2.7.11.26 tau-protein kinaseIUBMB Comments
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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- 2.7.11.26
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- diabetes
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- obesity
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- metformin
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proliferator-activated
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high-fat
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-
signal-regulated
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-
obese
-
diet-induced
- leptin
- myotubes
- sirt1
-
antidiabetic
-
element-binding
-
lipogenesis
-
hyperphosphorylation
- hypothalamic
-
insulin-stimulated
-
rho-associated
-
lipogenic
-
cardioprotective
-
hfd-induced
- carnitine
- sirtuins
- ripk1
-
receptor-interacting
- srebp-1c
- coactivator-1
-
monophosphate-activated
- biguanide
-
anti-obesity
-
necroptosis
- pharmacology
- medicine
- drug development
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
AMP-activated protein kinase, AMPK, AtK-1, brain proteinkinase PK40erk, cAMP-dependent protein kinase A, Cdk5, Cdk5-p25, Cdk5-p35, CDK5/p25, cyclin-dependent kinase 5, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AMP-activated protein kinase
AMPK
cAMP-dependent protein kinase A
Cdk5
cyclin-dependent kinase 5
Gasket protein
-
-
-
-
glycogen synthase kinase
-
-
-
-
glycogen synthase kinase 3
glycogen synthase kinase 3beta
glycogen synthase kinase-3
glycogen synthase kinase-3 alpha
glycogen synthase kinase-3alphabeta
glycogen synthase kinase-3beta
GSK-3
GSK-3 alpha
-
-
-
-
GSK-3 beta
GSK-3alpha
GSK-3beta
GSK-3beta1
GSK-3beta2
GSK3
GSK3alpha
GSK3beta
PKA
protein tau kinase
-
-
-
-
serine/threonine-protein kinase MDS1/RIM11
-
shaggy-related protein kinase theta
tau factor protein kinase (phosphorylating)
-
-
-
-
tau kinase
tau protein kinase
tau protein kinase I
tau protein kinase II system
tau tubulin kinase 2
tau-protein kinase I
tau-tubulin kinase
Tau-tubulin kinase 1
TPK
TPKI
TPKI/GSK-3beta
TPKI/GSK3beta
TTBK1
TTBK2
TTK
additional information
glycogen synthase kinase-3
-
-
glycogen synthase kinase-3beta
-
-
glycogen synthase kinase-3beta
-
-
glycogen synthase kinase-3beta
-
-
GSK-3 beta
-
-
-
-
GSK-3beta
-
-
GSK-3beta
-
-
tau kinase
-
-
-
-
tau protein kinase
-
-
-
-
tau protein kinase I
-
-
-
-
additional information
-
CDK5 is a unique member of the CDK family, see also EC 2.7.11.22
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + tau-protein = ADP + O-phospho-tau-protein
-
-
-
-
ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
-
-
-
-
ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
activation loop structure, substrate binding structure, and catalytic site structure and mechanism
-
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
-
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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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 + 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 + dephospho-beta-tubulin
ADP + beta-tubulin phosphate
-
isoenzyme tau-tubulin kinase
-
-
?
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
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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
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-
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
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regulates PDH and participates in energy metabolism and acetylcholine synthesis
-
?
ATP + protein tau
ADP + protein tau phosphate
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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
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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
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-
?
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
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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
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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
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-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
-
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
cdk5 associated with p25
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-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
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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]
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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 SUBSTRATE
NATURAL 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 + 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]
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]
-
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]
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 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]
-
-
-
?
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
?
-
-
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
?
-
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
?
-
-
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
?
-
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
?
-
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.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
661724, 662124, 662284, 662688, 662690, 662855, 693024, 693719, 693755, 702965, 703720, 704607, 705282, 705285, 705327, 705455, 705824, 705911, 740135, 741409, 741419
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
ATP
-
-
662302, 662673, 662686, 693729, 693777, 694359, 702959, 703088, 703234, 703942, 704493, 705251, 705253, 705453, 705898, 705942, 740410, 741440
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
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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.
INHIBITOR
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
-
-
N-[6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-methylpiperidine-1-carboxamide
-
-
N-[6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
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N-[6-(4-hydroxyphenyl)-5-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
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N-[6-(4-hydroxyphenyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
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N-[6-(4-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
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N-[6-(tetrahydrothiophen-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide
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Nicotine
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attenuates beta-amyloid peptide 1-42-induced activation of GSK-3beta
progesterone
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decreases expression and phosphorylation of GSK-3 beta in the cerebellum but not in the hypothalamus, regulation of tau expression and phosphorylation by progesterone may contribute to the hormonal regulation of cerebellar function by the modification of neuronal cytoskeleton
Protein kinase C
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protein kinase C inhibits GSK-3beta by phosphorylating its auto-inhibitory domain at Ser9
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TDZD-8
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selective GSK-3beta inhibitor, induces phosphorylation of the Ser9 residue, thereby inactivating GSK-3beta
ZM336372
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inhibits GSK-3beta through phosphorylation at Ser9, a dose-dependent increase in phosphorylation of GSK-3beta occurs after treatment with ZM336372 (0.025-0.1 mM)
[3R]-1-[5-methyl-7Hpyrrolo[2,3-d]pyrimidin-4-yl]pyrrolidin-3-amine
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enzyme binding structure analysis
ATP
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strongly inhibited by elevated concentrations of ATP uncomplexed with magnesium
ATP
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strongly inhibited by elevated concentrations of ATP uncomplexed with magnesium
CT99021
inhibition of GSK3 with CT99021 has little effect on the relative level of phosphorylation of Ser199 or Ser404 of human tau, but inhibition of GSK3beta using CT99021 results in dephosphorylation of endogenous c-Jun, Inh-2 and beta-catenin and dramatically increased c-Myc and beta-catenin expression
LiCl
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a dose-dependent increase in phosphorylation of GSK-3beta occurs after treatment with LiCl (5-20 mM)
LiCl
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pharmacological inhibition of GSK3 in old transgenic mice by chronic treatment with lithium, leads to a reduction of the age-dependent increase in tau hyperphosphorylation
LiCl
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lithium is a weak inhibitor of GSK3beta, lithium dose-dependently inhibits GSK3beta through the phosphorylation of serine 9 residue
lithium
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after inhibition of GSK-3 in cortical neurons, the splicing factor SC35 is nuclearly redistributed and enriched in nuclear speckles and colocalizes with the kinase
lithium
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selective inhibition of GSK-3, blocks tau hyperphosphorylation either in cultured neurons or in rat brain
roscovitine
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complete inhibition of T231 phosphorylation by 25-Cdk5 kinase complex
SB216763
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potent and selective cell permeable ATP-competitive inhibitor of GSK3
trans-activating transcriptor-eIF2B
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acts as a competitive inhibitor of GSK-3
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trans-activating transcriptor-eIF2B
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acts as a competitive inhibitor of GSK-3
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additional information
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phosphorylation of GSK3beta at S9 inhibits the enzyme
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additional information
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no inhibition of the p25-Cdk5 kinase complex by PD98059 and SB203580
-
additional information
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inhibition of GSK3 activity results in c-MYC activation, leading to the induction of Bax, Bim, DR4/DR5, and tumor necrosis factor-related apoptosis-inducing ligand expression and subsequent cytotoxicity. inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-kappaB activity. Inhibition of GSK3 activity results in c-MYC-dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways
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additional information
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not inhibited by 2-(2,3-dihydro-1-benzofuran-5-yl)-5-[(3-fluorobenzyl)oxy]-1,3,4-oxadiazole
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additional information
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galectin-3 regulates GSK-3beta activity/phosphorylation via the PI3K/AKT pathway
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additional information
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treatment with 1 CFU/cell bacillus Calmette-Guerin increases the phosphorylation of GSK3beta at serine 9 and therefore inhibits the activity to about 40% 1 h after stimulation
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additional information
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the crude organic extract of fermentation cultures of Streptomyces sp. strain H7667 inhibits growth of a yeast transformant (with cloned human GSK-3beta) at 37°C, but shows no inhibition at 25°C
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additional information
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design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3beta inhibitors. Compounds 3-(1-(3-morpholinopropyl)-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-pyrrol-3-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-(1-(3-hydroxypropyl)-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione, and 3-(1-methyl-1H-indol-3-yl)-4-(1H-pyrrol-3-yl)-1H-pyrrole-2,5-dione significantly reduce amyloidbeta-induced Tau hyperphosphorylation, showing the inhibition of GSK-3beta at the cellular level. Structure-activity relationships, in silico molecular modeling study, overview
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additional information
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inhibitor development using seven different scaffolds, scaffold 3-aminopyrrolidine exhibits high preferential affinity with GSK3beta. Interaction analysis of inhibitor scaffolds with different protein kinases, overview
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additional information
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activation of EphB2 receptor kinase arrests tau hyperphosphorylation through PI3K-/Akt-mediated GSK-3beta inhibition. EphrinB1/Fc treatment induces tyrosine phosphorylation (activation) of EphB2, while deletion of the tyrosine kinase domain (VM) of EphB2 eliminates the receptor stimulation-induced GSK-3beta inhibition and tau dephosphorylation
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additional information
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not inhibited by indirubin, indirubin-3'-oxime, 5-bromo-indirubin, 5-aminoindirubin-3'-oxime, 6-bromo-indirubin, 6-bromo-N-methyl-indirubin-3'-oxime, 6-bromo-N-methyl-indirubin-3'-acetoxime, 6-bromo-indirubin-3'diethyl phosphatoxime, indirubin-3'-methoxime, 6-bromo-5-nitroindirubin, 6-bromo-5-nitroindirubin-3'-oxime, and 6-bromo-5-methylindirubin
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additional information
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inactivating phosphorylation of Ser9 of TPKI/GSK3beta in close correspondence with tau phosphorylation
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additional information
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Cdk5 over-activation leads to inhibition of GSK3 in young transgenic mice, in old transgenic animals the inhibition of GSK3 is lost
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additional information
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N-terminus negatively regulates tau phosphorlyation by blocking GSK3beta access, local conformational change induced by T231 phosphorylation is required for the phosphorylation of the C-terminus and hyperphosphorylation of tau
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additional information
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cdk5 can negatively regulate GSK3beta activity through neuregulin/ErbB signaling, phosphorylation at the inhibitory GSK3beta-Ser9 site activates GSK3beta
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additional information
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the 3-nitropropionic acid treatment induces GSK-3beta truncation, calpeptin prevents GSK-3beta cleavage and cell death induced by 3-nitropropionic acid
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additional information
stimulation of EphB2 upregulates PI3K and Akt causing inhibition of GSK-3beta
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additional information
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protein tau-associated novel protein kinase Cepsilon suppresses the GSK-3beta-mediated phosphorylation of protein tau through the phosphorylation of GSK-3beta by the kinase in vitro
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additional information
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desacyl-carteriosulfonic acid shows no GSK-3beta inhibitory activity at concentrations up to 0.05 mM
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additional information
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phosphorylation of GSK3beta at S9 inhibits the enzyme, the phosphorylation at Ser9 is inhibited by wortmannin or GF-109203X, this inhibition is eliminated by inhibition of GSK-3 by a different inhibitor
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additional information
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GSK-3 is inactivated by phosphorylation of serine 9 in GSK-3beta and serine 21 in GSK-3alpha subunits by mainly Akt. Hyperglycemia induces strong activity of GSK-3 in rat brain
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additional information
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Galphaq protein inhibits GSK-3beta via activation of protein kinase C
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14-3-3
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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
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AT7519
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0.0005 mM AT7519 inhibits glycogen synthase kinase 3beta phosphorylation, AT7519 dephosphorylates GSK-3beta independent of inhibition of transcription
beta-amyloid peptide 1-42
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0.01 mM, induces phosphorylation at Tyr216 activating GSK-3beta
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cholesterol 3-sulfate
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potent stimulator for the GSK-3beta-mediated phosphorylation of tau protein (about 10fold stimulation in the presence of 0.003 mM)
cisplatin
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GSK-3 is activated by cisplatin treatment of HEI-OC1 cells, 0.02 mM cisplatin induces phosphorylation of Tyr216 GSK-3beta in HEI-OC1 cells but reduces the phosphorylation of Ser9 GSK-3beta, the activity of GSK-3beta is regulated negatively by the phosphorylation of Ser9 and positively by the phosphorylation of Tyr216
D-galactosylceramide-3-O-sulfate
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potent stimulator for the GSK-3beta-mediated phosphorylation of tau protein (about 11fold stimulation in the presence of 0.003 mM)
ether
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dramatic increase in the phosphorylation level of Ser9 of TPKI/GSK3beta immediately and 10 min after ether administration, followed by rapid virtual reversion to baseline by 20 min, no significant changes in the protein level or Tyr216 phosphorylation level of the enzyme
FRAT-2
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i.e. frequently rearranged in advanced T-cell lymphoma protein 2, activates phosphorylation of primed sites of tau protein about 8fold, no effect on unprimed site phosphorylation
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heparansulfate
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heparin is more effective than heparan sulfate at lower concentrations in inducing the hyperphosphorylation of tau by GSK3beta
p35
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tightly bound neuronal activator of cdk5, required for activity with regulatory function, p39 activates to a greater extent compared to p35 in vitro
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p39
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tightly bound neuronal activator of cdk5, required for activity with regulatory function, p39 activates to a greater extent compared to p35 in vitro, p39 is the activator activator in vivo
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syndapin 1
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highly stimulates the GSK-3beta-mediated phosphorylation of protein tau (about 4.3fold stimulation in the presence of 0.003 mM)
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AMP
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AMP binding induces a conformational change in the ? -subunit activation loop of the kinase that allows phosphorylation of the activating residue Thr172 by AMPK upstream kinases
forskolin
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forskolin specifically induces tau hyperphosphorylation by PKA at Ser214 resulting in increased phosphorylation at Ser199, Ser22, Ser396, and Ser404 in N2a/tau441 cells, forskolin has no effect on GSK-3
heparin
-
heparin is more effective than heparan sulfate at lower concentrations in inducing the hyperphosphorylation of tau by GSK3beta
p25
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inducible cytotoxic expression factor required for Cdk5 activity, formation of a complex with Cdk5, p25 overexpression increases tau phosphorylation rate
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p25
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cyclin activator, dependent on, over 10fold increase in activity of CDK5
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p25
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activator required for CDK5 activity, activation of CDK5 by p25 which is activated by cleavage of p35 to p25
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protein 14-3-3
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a dimeric scaffold protein, protein is absolutely required for connection by simultaneous binding of glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex
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protein 14-3-3
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protein 14-3-3 facilitates tau phosphorylation by SGK1 and regulates its subcellular localization
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soluble beta-amyloid oligomers
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activate GSK-3beta mediated tau phosphorylation and increase toxicity, reduced content of soluble, not insoluble, amyloid oligomers reduces the tau phosphorylation activity, specific antibodies can inhibit the activation, overview
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soluble beta-amyloid oligomers
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activate GSK-3beta mediated tau phosphorylation and increase toxicity, reduced content of soluble, not insoluble, amyloid oligomers reduces the tau phosphorylation activity, specific antibodies can inhibit the activation, overview
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tubulin
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stimulates phosphorylation of tau under the condition of microtubile formation
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additional information