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Enzyme Nomenclature
Information on EC 2.7.11.24 - mitogen-activated protein kinase
Word Map on EC 2.7.11.24
- 2.7.11.24
- neuron
- vascular
- inflammation
- endothelial
- fibroblast
- epithelial
- injury
- necrosis
- macrophage
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3-kinase
- adhesion
- carcinoma
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nf-kappab
- phosphatidylinositol
- arrest
- bone
- breast
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proinflammatory
- lipopolysaccharide
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oncogenic
- camp
- cardiac
- caspase-3
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phospholipase
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blockade
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tnf-alpha
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interleukin
- monocyte
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chemokine
- angiogenesis
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cyclins
- metastasis
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lps-induced
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phorbol
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dominant-negative
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metalloproteinase
- wortmannin
- cyclooxygenase-2
- angiotensin
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integrins
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neuroprotective
- phosphoinositide
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protein-coupled
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toll-like
- rapamycin
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platelet-derived
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factor-kappab
- osteoblast
- pertussis
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il-1beta
- analysis
- medicine
- drug development
- pharmacology
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.7.11.24
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RECOMMENDED NAME
GeneOntology No.
mitogen-activated protein kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a protein = ADP + a phosphoprotein
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ATP + a protein = ADP + a phosphoprotein
activation involves the activation loop, a polypeptide region outside the active site cleft, which is reversibly phosphorylated
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ATP + a protein = ADP + a phosphoprotein
the kinetics of p38 MAPK follow a rapid-equilibrium random-order ternary-complex mechanism, the enzyme is highly specific for Ser-Pro or Thr-Pro motifs
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKK-activated)
Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline [6]. A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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CAS REGISTRY NUMBER
COMMENTARY
142243-02-5
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
a mycoparasitic fungus of soilborne plant pathogens, e.g. S. rolfsii and R.solani, strain IMI 304061
SwissProt
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660948, 662107, 662678, 663620, 664568, 664618, 664687, 665638, 666322, 677890, 678159, 679691, 680896, 682741, 691266, 691301, 692440, 692625, 693505, 701309, 701666, 702513, 702561, 702574, 702641, 702692, 702942, 703019, 703255, 703561, 703573, 704471, 705276, 705321, 705322, 705447, 706080, 706863, 740242, 740720
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660948, 664067, 665052, 666322, 677321, 691878, 693135, 693384, 693778, 702065, 702156, 703166, 703715, 740424
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for binding studies the X-ray structure of murine p38alpha is used
SwissProt
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
evolution
the enzyme contains the conserved catalytic domain of the serine/threonine kinases
evolution
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the enzyme contains the conserved catalytic domain of the serine/threonine kinases
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malfunction
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MKKs 1 and 2 induce dual phosphorylation of the TEY motif in the activation loop of the kinase-death version of MPK4KD, but do not stimulate MPK4KD to phosphorylate myelin basic protein; MKKs 4 and 5 induce dual phosphorylation of the TEY motif in the activation loop of the kinase-death version of MPK3KD, but do not stimulate MPK3KD to phosphorylate myelin basic protein; MKKs 4 and 5 induce dual phosphorylation of the TEY motif in the activation loop of the kinase-death version of MPK6KD, but do not stimulate MPK6KD to phosphorylate myelin basic protein
malfunction
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pre-treatment of human synovial sarcoma cells with inhibitors of ERK1/2, p38 MAPK, and JNK attenuates the IL-17A-induced phosphorylation of activator protein-1 (AP-1) subunits and the expression of MMP-3 mRNA; pre-treatment of human synovial sarcoma cells with inhibitors of ERK1/2, p38 MAPK, and JNK attenuates the IL-17A-induced phosphorylation of activator protein-1 (AP-1) subunits and the expression of MMP-3 mRNA
malfunction
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inhibition of ERK MAPK activity increased E-cadherin expression at both the transcriptional and protein level. Knockdown of EKR1/2 expression by siRNA in A-549 cells produces a similar up-regulation of E-cadherin. Inhibition of p38 and ERK1/2 activities but not JNK and PI3K abrogates DU145 cells survival advantage; inhibition of p38 MAPK activity increased E-cadherin expression at both the transcriptional and protein level. Knockdown of p38alpha expression by siRNA in A-549 cells produces a similar upregulation of E-cadherin. Inhibition of p38 and ERK1/2 activities but not JNK and PI3K abrogates DU145 cells survival advantage
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
malfunction
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root elongation in seedlings of the loss-of-function mutants mpk6-2 and mpk6-3 is less sensitive to NaCl or Na-glutamate, but not to KCl or mannitol, as compared with that of wild-type seedlings. The tolerance of mpk6 to Na+ toxicity is Ca2+-dependent. At the plasma membrane, increased concentrations of NaCl increase the inward Na+-conducted currents while decreasing the outward Na+-conducted currents in wild-type root cells, attended by a positive shift in membrane potential. In mpk6 mutant root cells, NaCl significantly increases outward but not inward Na+-conducted currents, accompanied by a negative shift in membrane potential. Mutant mpk6 decreases NaCl-induced the Na+ accumulation by modifying PM Na+ flux in root cells. Mutant mpk6 accumulates less Na+ in response to NaCl because of the increased cytosolic Ca2+ level in root cells; thus, its root elongation is less inhibited than that of WT by NaCl
malfunction
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ERK inhibition using PD98059 causes reduction of wound healing by up to 15%; ERK inhibition using PD98059 causes reduction of wound healing by up to 15%; inhibition of JNK completely blocks mycosporine-like amino acids-mediated wound closure
malfunction
the mpk6-2 mutant is sensitive to 3-nitro-L-tyrosine (NO2-Tyr) treatment with respect to mitotic abnormalities, and root cells overexpressing the MAP kinase-inactivating phosphatase AP2C3 show defects in chromosome segregation and spindle orientation
malfunction
the enzyme knockout mutant shows colonies that are smaller and more compact thant the wild-type colonies. Additionally, while the wild-type produces abundant aerial hyphae on PDA plates, the mutant produces fewer and shorter aerial hyphae. Although mutation of the MAP kinase gene shows substantial effect on the fungal hyphal structure and colony morphology, the conidia produced by the mutant are similar to the wild-type with normal size and morphology. The mutant has reduced production of chitin and reduced expression levels of chitin biosynthetic genes. The mutant DELTAFoSlt2 shows lower chitin contents than wild-type and complemented strain DELTAFoSlt2-c. The mutant strain also shows reduced levels of different chitin syntases, overview. The mutant is sensitive to H2O2. The siderophore biosynthetic gene sidA is 2fold upregulated in mutant DELTAFoSlt2. The expression levels of beauvericin biosynthetic genes, beas, kivr and abc3, are significantly reduced in mutants DELTAFoSlt2 by 12fold, 4fold, and 5fold, respectively as compared to the wild-type, while the expression of fusaric acid biosynthetic genes FUB1 to FUB5 is significantly reduced in the mutant by 100fold, 11fold, 10fold, 25fold, and 50fold, respectively. Hyphal growth rates of the mutant DELTAFoSlt2 is reduced on solid media but not affected in liquid media
malfunction
no morphological changes are observed in the DELTACshog1 knockout mutant in comparison with the wild-type, but they are slightly reduced in growth under oxidative stress and are hypersensitive to hyperosmotic stress. The DELTACshog1 mutants form normal appressoria-like structures but are reduced in virulence when inoculated on Bowman leaves. The DELTACshog1 mutant is able to infect barley roots, no significant difference in virulence is observed for DELTACshog1 mutants compared to the wild-type; the DELTACsfus3 knockout mutant is defective in conidiation and formation of appressoria-like structures, showing hypersensitivity to oxidative stress and loss of pathogenicity on non-wounded leaves of Hordeum vulgare cv. Bowman. When inoculated on wounded leaves of Bowman, the DELTACsfus3 knockout mutant is reduced in virulence compared to the wild-type. The DELTACsfus3 mutant fails to cause any symptoms on barley roots; the DELTACsslt2 knockout mutant produces more vegetative hyphae, has lighter pigmentation, are more sensitive to cell wall degrading enzymes, and are reduced in virulence on Bowman leaves compared to the wild-type, although they formed normal appressoria like the wild-type. The DELTACsslt2 mutant is able to infect barley roots. DELTACsslt2 mutants show significantly reduced virulence on barley roots in comparison with the wild-type
malfunction
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root elongation in seedlings of the loss-of-function mutants mpk6-2 and mpk6-3 is less sensitive to NaCl or Na-glutamate, but not to KCl or mannitol, as compared with that of wild-type seedlings. The tolerance of mpk6 to Na+ toxicity is Ca2+-dependent. At the plasma membrane, increased concentrations of NaCl increase the inward Na+-conducted currents while decreasing the outward Na+-conducted currents in wild-type root cells, attended by a positive shift in membrane potential. In mpk6 mutant root cells, NaCl significantly increases outward but not inward Na+-conducted currents, accompanied by a negative shift in membrane potential. Mutant mpk6 decreases NaCl-induced the Na+ accumulation by modifying PM Na+ flux in root cells. Mutant mpk6 accumulates less Na+ in response to NaCl because of the increased cytosolic Ca2+ level in root cells; thus, its root elongation is less inhibited than that of WT by NaCl
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malfunction
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no morphological changes are observed in the DELTACshog1 knockout mutant in comparison with the wild-type, but they are slightly reduced in growth under oxidative stress and are hypersensitive to hyperosmotic stress. The DELTACshog1 mutants form normal appressoria-like structures but are reduced in virulence when inoculated on Bowman leaves. The DELTACshog1 mutant is able to infect barley roots, no significant difference in virulence is observed for DELTACshog1 mutants compared to the wild-type; the DELTACsfus3 knockout mutant is defective in conidiation and formation of appressoria-like structures, showing hypersensitivity to oxidative stress and loss of pathogenicity on non-wounded leaves of Hordeum vulgare cv. Bowman. When inoculated on wounded leaves of Bowman, the DELTACsfus3 knockout mutant is reduced in virulence compared to the wild-type. The DELTACsfus3 mutant fails to cause any symptoms on barley roots; the DELTACsslt2 knockout mutant produces more vegetative hyphae, has lighter pigmentation, are more sensitive to cell wall degrading enzymes, and are reduced in virulence on Bowman leaves compared to the wild-type, although they formed normal appressoria like the wild-type. The DELTACsslt2 mutant is able to infect barley roots. DELTACsslt2 mutants show significantly reduced virulence on barley roots in comparison with the wild-type
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malfunction
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the enzyme knockout mutant shows colonies that are smaller and more compact thant the wild-type colonies. Additionally, while the wild-type produces abundant aerial hyphae on PDA plates, the mutant produces fewer and shorter aerial hyphae. Although mutation of the MAP kinase gene shows substantial effect on the fungal hyphal structure and colony morphology, the conidia produced by the mutant are similar to the wild-type with normal size and morphology. The mutant has reduced production of chitin and reduced expression levels of chitin biosynthetic genes. The mutant DELTAFoSlt2 shows lower chitin contents than wild-type and complemented strain DELTAFoSlt2-c. The mutant strain also shows reduced levels of different chitin syntases, overview. The mutant is sensitive to H2O2. The siderophore biosynthetic gene sidA is 2fold upregulated in mutant DELTAFoSlt2. The expression levels of beauvericin biosynthetic genes, beas, kivr and abc3, are significantly reduced in mutants DELTAFoSlt2 by 12fold, 4fold, and 5fold, respectively as compared to the wild-type, while the expression of fusaric acid biosynthetic genes FUB1 to FUB5 is significantly reduced in the mutant by 100fold, 11fold, 10fold, 25fold, and 50fold, respectively. Hyphal growth rates of the mutant DELTAFoSlt2 is reduced on solid media but not affected in liquid media
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metabolism
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endoplasmic reticulum homeostasis is regulated by a network of signaling pathways which include stearoyl-CoA desaturase (SCD)-1, p38 mitogen-activated protein kinase (MAPK) and the unfolded protein response (UPR). All these pathways are located at the interface of cell cycle control and cell stress. Inhibition or silencing of SCD-1, via inhibitor CAY10566 or siRNA, specifically induces phosphorylation and activation of p38 MAPK. SCD-1 counteracts palmitate-induced endoplasmic reticulum stress by reducing p38 MAPK activation. Role of SCD-1 and p38 MAPK for neutral lipid biosynthesis, cell proliferation, and viability and insulin-dependent glucose uptake, overview
metabolism
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hepatocyte coculture induces the re-expression of E-cadherin via abrogation of autocrine EGFR signaling pathway in prostate cancer (PCa) cells and this confers a survival advantage. Hepatocytes educate PCa cells to undergo mesenchymal to epithelial reverting transition (MErT) by modulating the activity of p38 and ERK1/2. Hepatocytes inhibit p38 and ERK1/2 activity in prostate cancer cells, which allows E-cadherin re-expression. Introduction of constitutively active MEK6 and MEK1 to DU-145 cells cocultured with hepatocytes abrogates E-cadherin re-expression. At least a partial phenotypic reversion can be achieved by suppression of p38 and ERK1/2 activation in DU-145 cells even in the absence of hepatocytes
metabolism
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MAPK cascade proteins bind to each other selectively via docking interactions; MAPK cascade proteins bind to each other selectively via docking interactions. The high selectivity of JNK family MAPKs for cognate binding partners is controlled by two key hydrophobic residues in the docking site; MAPK cascade proteins bind to each other selectively via docking interactions. The high selectivity of JNK family MAPKs for cognate binding partners is controlled by two key hydrophobic residues in the docking site
metabolism
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MAPK cascade proteins bind to each other selectively via docking interactions
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
metabolism
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mycosporine-like amino acids promote wound healing through focal adhesion kinase (FAK, EC 2.7.10.2) and mitogen-activated protein kinases (MAP kinases) signaling pathway in keratinocytes; mycosporine-like amino acids promote wound healing through focal adhesion kinase (FAK, EC 2.7.10.2) and mitogen-activated protein kinases (MAP kinases) signaling pathway in keratinocytes; mycosporine-like amino acids promote wound healing through focal adhesion kinase (FAK, EC 2.7.10.2, HaCaT cells) and mitogen-activated protein kinases (MAP kinases) signaling pathway in keratinocytes
metabolism
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pathogen-associated molecular patterns (PAMPs) are recognized by plant pattern recognition receptors to activate PAMP-triggered immunity. PAMP perception enhances phosphorylation of BES1. BES1 is a unique direct substrate of MPK6 in PAMP-triggered immunity signaling. MAPK-mediated BES1 phosphorylation is another BES1 modulation mechanism in plant cell signaling, in addition to GSK3-like kinase-mediated BES1 phosphorylation and F box protein-mediated BES1 degradation. BES1 phosphorylation induced by flg22 occurs downstream of MAPK activation. MKK5K99M acts as a dominant negative mutant that partially blocks MAPK activation and downstream PTI signaling
metabolism
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pathogen-associated molecular patterns (PAMPs) are recognized by plant pattern recognition receptors to activate PAMP-triggered immunity. PAMP perception enhances phosphorylation of BES1. BES1 is a unique direct substrate of MPK6 in PAMP-triggered immunity signaling. MAPK-mediated BES1 phosphorylation is another BES1 modulation mechanism in plant cell signaling, in addition to GSK3-like kinase-mediated BES1 phosphorylation and F box protein-mediated BES1 degradation. BES1 phosphorylation induced by flg22 occurs downstream of MAPK activation. MKK5K99M acts as a dominant negative mutant that partially blocks MAPK activation and downstream PTI signaling
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physiological function
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JNK1 disrupts the insulin signaling cascade via phosphorylation of the insulin receptor substrate IRS-1, which leads to the degradation of IRS-1
physiological function
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JNK1 has been suggested to play a central role in the development of obesity-induced insulin resistance; JNK3 has been shown to mediate neuronal apoptosis
physiological function
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p38alpha mitogen-activated protein kinase is involved in the signaling cascade responsible for the development of inflammation, increased activity of the p38 enzyme results in cytokine overproduction
physiological function
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the MAPK pathway, via the Ras/Raf/MEK/ERK signal cascade, is responsible for transmitting and amplifying mitogenic signals from the cell surface to the nucleus where activated transcription factors regulate gene expression and determine cell fate
physiological function
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the MAPK pathway is important for cell proliferation, survival and differentiation
physiological function
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monocyte, macrophage production of tumor necrosis factor-alpha is largely driven by p38 mitogen-activated protein kinase
physiological function
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the mitogen-activated protein kinase signaling pathway is one of the major second messenger systems regulating glutamate release at the presynaptic level
physiological function
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the JNKs signal transduction pathway plays an important role in coordinating cellular responses including apoptosis, proliferation, and neoplastic transformation
physiological function
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the JNKs signal transduction pathway plays an important role in coordinating cellular responses including apoptosis, proliferation, and neoplastic transformation
physiological function
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p38 alpha mitogen-activated protein kinase is a key component of the cascade leading to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1beta
physiological function
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pERK1/2 appears to specifically modulate gating properties of Na(v)1.7, an effect that may contribute to the role of this channel in dorsal root ganglion neuron excitability
physiological function
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signal transduction through the p38 mitogen-activated protein kinase pathway is central to the transcriptional and translational control of cytokine and inflammatory mediator production
physiological function
ERK2 is a critical component in the mitogen-activated protein kinase signal cascade, where it helps regulate many cellular processes including proliferation, differentiation, and survival
physiological function
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essential role of mitogen-activated protein kinases in IL-17A-induced matrix metalloproteinase MMP-3 expression in human synovial sarcoma cells, overview; essential role of mitogen-activated protein kinases in IL-17A-induced matrix metalloproteinase MMP-3 expression in human synovial sarcoma cells, overview. IL-17A induces MMP-1 and MMP-9 via ERK1/2 and p38 MAPK-dependent activation of the transcriptional factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB); essential role of mitogen-activated protein kinases in IL-17A-induced matrix metalloproteinase MMP-3 expression in human synovial sarcoma cells, overview. IL-17A induces MMP-1 and MMP-9 via ERK1/2 and p38 MAPK-dependent activation of the transcriptional factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB)
physiological function
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role of p38 mitogen-activated protein kinase in linking stearoyl-CoA desaturase-1 activity with endoplasmic reticulum homeostasis. During lipotoxic and cell cycle stress, prolonged activation of p38 MAPK due to SCD-1 inhibition induced endoplasmic reticulum stress, the unfolded protein response, and endoplasmic reticulum/Golgi remodeling. The negative regulation of p38 MAPK mediates the protective effects of SCD-1 on endoplasmic reticulum homeostasis under distinct stress conditions. Role of SCD-1 and p38 MAPK for neutral lipid biosynthesis, cell proliferation, and viability and insulin-dependent glucose uptake, overview
physiological function
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mitogen-activated protein kinases (MAPKs) are important components of the tripartite mitogen-activated protein kinase signaling cascade and play an important role in plant growth and development. Involvement of specific MAPK family members in different stages of fruit ripening, overview. Some MaMPKs might be negatively regulated by ethylene, their expression increases in post-ethylene. MaMPKs might play an important role in senescence or in the response to pathogen stress, as at this stage of ripening, fungal infection begins to take place
physiological function
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dual specificity phosphatases play a crucial role in MAP kinase regulation. Dual specificity phosphatase DUSP16 (MKP7) and p38alpha interact in a unique manner that is different from other dual specificity phosphatases, DUSP16 binds p38alpha via an extended binding surface that includes helix alpha4. KIM-containing MAPK-specific dual specificity phosphatase DUSP10 also uses a unique binding mode to interact with p38alpha. The interaction of the MAPK binding domain of DUSP16 with p38alpha shows that despite belonging to the same dual specificity phosphatase (DUSP) family, its interaction mode differs from that of DUSP10, detailed overview. DUSP16 selectively inactivates JNK and p38 following stress activation
physiological function
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the intrinsic activity of wild-type p38beta is regulated in mammalian cells
physiological function
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the p38gamma C-terminus is an efficient inducer of cell death after its intracellular delivery. Binding of the C-terminal sequence of p38gamma to PTPN4 abolishes the catalytic autoinhibition of PTPN4 and thus activates the phosphatase, which can efficiently dephosphorylate the activation loop of p38gamma. The p38gamma-PTPN4 interaction promotes cellular signaling, preventing cell death induction
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
physiological function
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mitogen-activated protein kinase 6 controls root growth in Arabidopsis thaliana by modulating Ca2+-based Na+ flux in root cell under salt stress
physiological function
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JNK is a factor involved in inflammation, proliferation, and apoptosis. In addition JNK is essential for cell migration and keratinocyte movement through phosphorylation of paxillin. Activation of JNK1 is involved in wound repair. The activation of JNK is involved in the mycosporine-like amino acid-induced cell migration
physiological function
the active form of MAP kinase interacts with gamma-tubulin on specific subsets of mitotic microtubules during late mitosis. MPK6 phosphorylates EB1c, but not EB1a, and has a role in maintaining regular planes of cell division under stress conditions. MPK6 activtes the micotubule-associated protein MAP65-1 that has a redundant function in Arabidopsis with MAP65-3 in cytokinesis. MPK6 is required for regulation of the alignment of cell division on NO2-Tyr treatment
physiological function
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brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, BES1, is phosporylted by Arabidospis thaliana MPK6. MAPK-mediated phosphorylation alters BES1 subcellular accumulation in PAMP-triggered immunity
physiological function
effect of EGF-mediated mitogen-activated protein kinases 3 and 1 (MAPK3/1) pathway on in vitro cytoplasmic maturation of sheep oocytes, overview. The key downstream effectors of EGFR signaling in cumulus cells, mitogen-activated protein kinases 3 and 1 (MAPK3/1, also known as ERK1/2), is essential for mammalian oocyte maturation. Maturation of mammalian oocytes is a complex and dynamic process involving the maturation of nucleus and cytoplasm; effect of EGF-mediated mitogen-activated protein kinases 3 and 1 (MAPK3/1) pathway on in vitro cytoplasmic maturation of sheep oocytes, overview. The key downstream effectors of EGFR signaling in cumulus cells, mitogen-activated protein kinases 3 and 1 (MAPK3/1, also known as ERK1/2), is essential for mammalian oocyte maturation. Maturation of mammalian oocytes is a complex and dynamic process involving the maturation of nucleus and cytoplasm
physiological function
the enzyme is involved in siderophore biosynthesis and plays a vital role in regulation of fusaric acid production. The MAP kinase is necessary for the fungal virulence on banana plants and is required for the full virulence of Fusarium oxysporum f. sp. cubense
physiological function
the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants; the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants; the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants. Enzyme CsSLT2 has a role in the maintenance of cell-wall integrity in Bipolaris sorokiniana
physiological function
-
brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, BES1, is phosporylted by Arabidospis thaliana MPK6. MAPK-mediated phosphorylation alters BES1 subcellular accumulation in PAMP-triggered immunity; mitogen-activated protein kinase 6 controls root growth in Arabidopsis thaliana by modulating Ca2+-based Na+ flux in root cell under salt stress
-
physiological function
-
the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants; the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants; the MAPK gene is involved in the regulation of fungal development under normal and stress conditions and is required for full virulence on barley plants. Enzyme CsSLT2 has a role in the maintenance of cell-wall integrity in Bipolaris sorokiniana
-
physiological function
-
the enzyme is involved in siderophore biosynthesis and plays a vital role in regulation of fusaric acid production. The MAP kinase is necessary for the fungal virulence on banana plants and is required for the full virulence of Fusarium oxysporum f. sp. cubense
-
additional information
structure-based assignment of Ile, Leu, and Val methyl groups in the active and inactive forms of extracellular signal-regulated kinase 2, overview
additional information
-
residue Y119 is the gatekeeper in the MPK3 enzyme structure; residue Y124 is the gatekeeper in the MPK4 enzyme structure; residue Y144 is the gatekeeper in the MPK6 enzyme structure
additional information
-
p38 MAPK might show selective protein-lipid interactions
additional information
-
regulation of MAPKs is achieved via a plethora of regulatory proteins including activating MAPKKs and an abundance of deactivating phosphatases. Although all regulatory proteins use an identical interaction site on MAPKs, the common docking and hydrophobic pocket, they use distinct kinase interaction motif (KIM or D-motif) sequences that are present in linear, peptide-like, or well folded protein domains. Fine-tuning necessary to achieve MAPK specificity and regulation among multiple regulatory proteins
additional information
-
MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The D-sites of the p38 activators MKK3 and MKK6 both contain LXI in the first 3 residues of the hydrophobic submotif
additional information
-
MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The D-sites of the ERK pathway activators MEK1 and MEK2 contain IXL and LXI, respectively, in the first 3 residues of the hydrophobic submotif
additional information
-
molecular basis of the interaction of the human protein tyrosine phosphatase non-receptor type 4 (PTPN4) with the mitogen-activated protein kinase p38gamma, the main contribution to the p38gamma-PTPN4 complex formation is the tight interaction between the C-terminus of p38gamma and the PDZ domain of PTPN4, overview. NMR titration study at pH 7.5, 25�C
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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 + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
ATP + Arabidopsis thaliana protein AT1G7815
ADP + phosphorylated Arabidopsis thaliana proteins AT1G78150
-
-
-
-
?
ATP + Arabidopsis thaliana protein AT2G26530
ADP + phosphorylated Arabidopsis thaliana proteins AT2G26530
-
-
-
-
?
ATP + Arabidopsis thaliana protein AT3G11330
ADP + phosphorylated Arabidopsis thaliana proteins AT3G11330
-
-
-
-
?
ATP + Arabidopsis thaliana protein AT4G38710
ADP + phosphorylated Arabidopsis thaliana proteins AT4G38710
-
-
-
-
?
ATP + ATF2
ADP + a phosphorylated ATF2
-
substrate in assay, biotinylated ATF2
-
-
-
ATP + c-Jun transcription factor
ADP + phosphorylated c-Jun transcription factor
-
JNK phosphorylates the N-terminal transactivation domain of c-Jun transcription factor
-
-
?
ATP + DNA polymerase II
ADP + phosphorylated DNA polymerase II
-
substrate of Hog1p
-
-
?
ATP + FITC-Aca-Ala-Ala-Ala-Thr-Gly-Pro-Leu-Ser-Pro-Gly-Pro-Phe-Ala-NH2
ADP + phosphorylated FITC-Aca-Ala-Ala-Ala-Thr-Gly-Pro-Leu-Ser-Pro-Gly-Pro-Phe-Ala-NH2
-
FITC-labeled ERK substrate peptide
-
-
?
ATP + focal adhesion kinase
ADP + phosphorylated focal adhesion kinase
-
phosphorylation of FAK at S910, which promotes the disassembly of focal adhesion (hemidesmosome disruption) during cell migration
-
-
?
ATP + Gic2
ADP + phosphorylated Gic2
-
substrate of Fus3, and of Hog1
-
-
?
ATP + GLH-1
ADP + phosphorylated GLH-1
-
-
-
?
ATP + GST-c-Jun
ADP + phosphorylated GST-c-Jun
-
substrate in kinase activity assay
-
-
?
ATP + IRS-1
ADP + phosphorylated IRS-1
-
phosphorylation of the insulin receptor substrate IRS-1 at serine 307
-
-
?
ATP + MAP65-1
ADP + phosphorylated MAP65-1
microtubule-associated protein, phosphorylation in vitro by MPK6, recombinant GST-tagged substrate protein
-
-
?
ATP + MAPKAPK2-peptide
ADP + phosphorylated MAPKAPK2-peptide
-
the peptide substrate is derived from a sequence of a mitogen-activated protein kinase activated protein kinase-2, MAPKAPK2, phopshorylation site
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
-
binding to ERK requires docking domain and the kinase interaction motif
-
?
ATP + Mps1
ADP + phosphorylated Mps1
-
Mps1 phosphorylation by MAPK at S844, spindle checkpoint requires phosphorylation at S844, may create a phosphoepitope that allows Mps1 to interact with kinetochores
-
-
?
ATP + myelin basic protein
ADP + a phosphorylated myelin basic protein
-
substrate in kinase assay
-
-
?
ATP + protein EGFRP
ADP + phosphorylated protein EGFRP
-
epidermal growth factor receptor peptide, substrate in kinase activity assay
-
-
?
ATP + protein tyrosine kinase 2
ADP + phosphorylated protein tyrosine kinase 2
-
substrate of Hog1
-
-
?
ATP + RAD9
ADP + phospho-RAD9
-
high activity with Fus3, low activity with Hog1
-
-
?
ATP + RSK
ADP + phosphorylated RSK
-
-
binding to ERK requires docking domain
-
?
ATP + sodium channel Na(v)1.6
ADP + phosphorylated sodium channel Na(v)1.6
-
-
-
-
?
ATP + sodium channel Na(v)1.7
ADP + phosphorylated sodium channel Na(v)1.7
-
-
-
-
?
ATP + sodium channel Na(v)1.8
ADP + phosphorylated sodium channel Na(v)1.8
-
-
-
-
?
ATP + transcription factor ATF2
ADP + phosphorylated transcription factor ATF2
-
-
-
-
-
ATP + transcription factor Djun
ADP + phosphorylated transcription factor Djun
-
-
-
-
-
ATP + transcription factor Elk-1
ADP + phosphorylated transcription factor Elk-1
-
-
-
-
-
ATP + transcription factor SAP-1
ADP + phosphorylated transcription factor SAP-1
-
-
-
-
-
ATP + WRKY25
ADP + phosphorylated WRKY25
-
the transcription factor is an in vitro substrate of MPK4
-
-
?
ATP + WRKY33
ADP + phosphorylated WRKY33
-
the transcription factor is an in vitro substrate of MPK4
-
-
?
ATPgammaS + myelin basic protein
ADP + thiophosphorylated myelin basic protein
-
Arabidopsis thaliana MPKs use ATPgammaS to thiophosphorylate myelin basic protein
-
-
?
N6-benzyl-ATPgammaS + myelin basic protein
ADP + benzylthiophosphorylated myelin basic protein
-
Arabidopsis thaliana MPK3 mutant T119A uses N6-benzyl-ATPgammaS to thiophosphorylate myelin basic protein
-
-
?
phosphoprotein
?
-
the MAPK is regulated in the MAPK signaling cascade by 2 mechanisms: 1. by MEK, EC 2.7.11.25, docking at the allosteric ED domain or the CD domain of MAPKs, or 2. by MKK7, MLK, JNK or MKP-7 docking at the scaffolding protein JIP in the JNK signaling pathway
-
-
-
ATP + a protein
ADP + a phosphoprotein
-
ERK2 phosphorylates MBP, p38 phosphorylates the protein substrate MAPKAP2 and the peptide substrate KRELVEPLTPSGEAPNQALLR, other substrates of MAPK are transcription factors, such as c-Jun, ATF-2, and MEF2A
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
662678, 701666, 702513, 702561, 702574, 702615, 702641, 702692, 702942, 703019, 703255, 703573, 704471, 705046, 705276, 705321, 705447, 706080, 706863, 703715
-
-
?
ATP + a protein
ADP + a phosphoprotein
MAPK activate mitogen-activated proteins in several signal transduction pathways, overview
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
-
?
ATP + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
-
ATF2
-
-
?
ATP + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
-
ATF2, recombinant GST-tagged ATF2DELTA115
-
-
?
ATP + AP1
ADP + phosphorylated AP1
-
substrate of ERK1/2, ERK access to the substrate is regulated by the all-trans retinoic acid receptor, RAR
-
-
?
ATP + ATF-2
ADP + phosphorylated ATF-2
-
assay substrate biotinylated ATF-2
-
-
?
ATP + ATF2
ADP + phosphorylated ATF2
-
substrate in in vitro kinase assay, LanthaScreen
-
-
?
ATP + ATF2
ADP + phosphorylated ATF2
phosphorylation by p38 MAPK at threonine residues
-
-
?
ATP + BES1
ADP + phosphorylated BES1
-
i.e. brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, an Arabidospis thaliana transcription factor. S286 and S137 residues are required for flg22-induced BES1 full phosphorylation in vivo, in which S286 plays a greater role than S137
-
-
?
ATP + BES1
ADP + phosphorylated BES1
-
i.e. brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, an Arabidospis thaliana transcription factor
-
-
?
ATP + BES1
ADP + phosphorylated BES1
-
i.e. brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, an Arabidospis thaliana transcription factor. S286 and S137 residues are required for flg22-induced BES1 full phosphorylation in vivo, in which S286 plays a greater role than S137
-
-
?
ATP + BES1
ADP + phosphorylated BES1
-
i.e. brassinosteroid insensitive1-ethyl methanesulfonate-suppressor1, an Arabidospis thaliana transcription factor
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
substrate of JNK, binding via delta domain of c-Jun substrate
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
the reaction is performed by activated phosphorylated ERK2
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
the reaction is performed by activated phosphorylated JNK3
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
recombinant GST-tagged substrate, the reaction is performed by activated phosphorylated ERK2
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
recombinant GST-tagged substrate, the reaction is performed by activated phosphorylated JNK3
-
-
?
ATP + c-Jun activation domain
ADP + phosphorylated c-Jun activation domain
-
enzyme binds to the c-Jun transactivation domain and phosphorylates it on Ser63 and Ser73
-
-
-
ATP + c-Jun activation domain
ADP + phosphorylated c-Jun activation domain
-
JNK2 binds c-Jun approximately 25 times more efficiently than JNK1
-
-
-
ATP + EB1c
ADP + phosphorylated EB1c
the microtubule plus end protein
-
-
?
ATP + EB1c
ADP + phosphorylated EB1c
the microtubule plus end protein, recombinant GST-tagged substrate protein, phosphorylation on a threonine residue
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
-
an ETS family transcription factor
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
-
an ETS family transcription factor with modified D-site by swapping two hydrophobic residues
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
-
an ETS family transcription factor
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
-
recombinant GST-tagged Elk1, substrate of ERK2
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
the reaction is performed by activated phosphorylated ERK2
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
the reaction is performed by activated phosphorylated JNK3
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
recombinant GST-tagged substrate, the reaction is performed by activated phosphorylated ERK2
-
-
?
ATP + Elk1
ADP + phosphorylated Elk1
recombinant GST-tagged substrate, the reaction is performed by activated phosphorylated JNK3
-
-
?
ATP + Hot1p
ADP + phosphorylated Hot1p
-
substrate of Hog1p, phosphorylation of Hot1p is not required for Hot1p-mediated gene expression
-
-
?
ATP + human glucocorticoid receptor
ADP + phosphorylated human glucocorticoid receptor
-
specific phosphorylation at Ser211 by p38 MAPK, p38 MAPK is a mediator in glucocorticoid-induced apoptosis of lymphoid cells, interaction of MAPK and glucocorticoid pathways, overview
-
-
?
ATP + human glucocorticoid receptor
ADP + phosphorylated human glucocorticoid receptor
-
specific phosphorylation at Ser211 by p38 MAPK
-
-
?
ATP + Lin-1
ADP + phosphorylated Lin-1
substrate of ERK2, negative regulation of Lin-1
-
-
?
ATP + Lin-1
ADP + phosphorylated Lin-1
Lin-1 is an ETS transcription factor, substrate of ERK2, binding via the docking sequence of the substrate
-
-
?
ATP + MKS1
ADP + phosphorylated MSK1
-
MPK4 acts as a regulator of pathogen defense responses and is required for repression of salicylic acid-dependent resistance and for activation of jasmonate-dependent defense gene expression via MSK1, which interacts with the transcription factors WRKY25 and WRKY33
-
-
?
ATP + MMP-9
ADP + phosphorylated MMP-9
-
activity of p38 MAP kinase, TNF-alpha stimulates MMP-9 expression via the p38 MAP kinase signaling pathway in 5637 cells, and p38 MAP kinase-mediated MMP-9 gene regulation in response to TNF-alpha is involved in the NF-kappaB response element in 5637 cells, regulation, overview
-
-
?
ATP + multifunctional protein CAD
ADP + phosphorylated multifunctional protein CAD
-
CAD initiates and regulates de novo pyrimidine biosynthesis and is activated by phosphorylation at Thr456 by nuclear MAPKs, nuclear import of CAD is required for optimal cell growth
-
-
?
ATP + multifunctional protein CAD
ADP + phosphorylated multifunctional protein CAD
-
phosphorylation at Thr456, native and recombinant CAD
-
-
?
ATP + multifunctional protein CAD
ADP + phosphorylated multifunctional protein CAD
-
CAD initiates and regulates de novo pyrimidine biosynthesis and is activated by phosphorylation at Thr456 by nuclear MAPKs, nuclear import of CAD is required for optimal cell growth
-
-
?
ATP + multifunctional protein CAD
ADP + phosphorylated multifunctional protein CAD
-
phosphorylation at Thr456, native and recombinant multifunctional protein CAD
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
substrate in in vitro kinase assay
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
substrate of ERK2
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
ATP + Net
ADP + phosphorylated Net
-
an ETS family transcription factor with modified D-site by swapping two hydrophobic residues
-
-
?
ATP + phospholipase C-gamma1
ADP + phosphorylated phospholipase C-gamma1
the reaction is performed by activated phosphorylated ERK2, phosphorylation inhibits phospholipase C-gamma1
-
-
?
ATP + phospholipase C-gamma1
ADP + phosphorylated phospholipase C-gamma1
recombinant substrate, the reaction is performed by activated phosphorylated ERK2
-
-
?
ATP + protein
ADP + phosphoprotein
-
autophosphorylates both Thr and Tyr residues
-
-
-
ATP + protein
ADP + phosphoprotein
autophosphorylation
-
-
-
ATP + protein
ADP + phosphoprotein
proline-directed kinase
-
-
-
ATP + protein
ADP + phosphoprotein
-
autophosphorylation on both tyrosine and threonine residues, autophosphorylation is probably involved in the MAP kinase activation process in vitro, but it may not be sufficient for full activation
-
-
-
ATP + protein ATF2
ADP + phosphorylated protein ATF2
-
recombinant GST-tagged ATF2 substrate
-
-
?
ATP + protein ATF2
ADP + phosphorylated protein ATF2
-
recombinant GST-tagged ATF2DELTA115
-
-
?
ATP + Smad1
ADP + phosphorylated Smad1
-
the MAP kinase antagonizes Smad1 in signaling during development of axis and neural specification, Smad1 is involved in dorsal-ventral patterning in embryos
-
-
?
ATP + Smad1
ADP + phosphorylated Smad1
-
phosphorylation by MAP kinase inhibits Smad1 and the BMP-4/Smad1 signaling pathway, phosphorylation sites are S187, S195, S205, and S213, activity with Smad1 mutant S187/S195/S205/S213, overview
-
-
?
ATP + Smad3
ADP + phosphorylated Smad3
-
substrate of MAPKs, e.g. ERK2, identification of phosphorylation sites Ser203, Ser207, and Thr187, Ser207 is the best phosphorylation site for ERK2, other MAPKs than ERK2 also phosphorylate Ser212
-
-
?
ATP + Ste50
ADP + phosphorylated Ste50
Hog1 phosphorylates Ste50 in response to osmotic stress, and phosphorylation of Ste50 limits the duration of Kss1 activation and prevents invasive growth under high osmolarity growth conditions. The feedback phosphorylation event leads to more transient activation of Hog1, regulation, overview
-
-
?
ATP + Ste50
ADP + phosphorylated Ste50
Hog1 phosphorylates Ste50 in response to osmotic stress, and phosphorylation of Ste50 limits the duration of Kss1 activation and prevents invasive growth under high osmolarity growth conditions. The feedback phosphorylation event leads to more transient activation of Kss1, regulation, overview
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
-
phosphorylation of tyrosine hydroxylase at Ser8 and Ser31 by ERK1 and ERK2 is involved in regulation of catecholamine biosynthesis
-
-
?
ATP + tyrosine hydroxylase
ADP + phosphorylated tyrosine hydroxylase
-
recombinant rat wild-type and S8A, S31A, S19A, and S40A mutant tyrosine hydroxylase substrates, phosphorylation at Ser8 and Ser31 by ERK1 and ERK2, ERK2 prefers the Ser31 phosphorylation site, no activity with substrate mutant S8A/S31A
-
-
?
additional information
?
-
-
FLAG-tagged Arabidopsis thaliana proteins AT1G78150, AT2G26530, AT3G11330, and AT4G38710 are good MPK3/6 substrates, but are poor substrates for the closely related Arabidopsis thaliana MPK4
-
-
-
additional information
?
-
-
MPK6 interacts with gamma-tubulin and co-sediments with plant microtubules polymerized in vitro. The active form of MAP kinase is enriched with microtubules and follows similar dynamics to gamma-tubulin, moving from poles to midzone during the anaphase-to-telophase transition
-
-
-
additional information
?
-
MPK6 interacts with gamma-tubulin and co-sediments with plant microtubules polymerized in vitro. The active form of MAP kinase is enriched with microtubules and follows similar dynamics to gamma-tubulin, moving from poles to midzone during the anaphase-to-telophase transition
-
-
-
additional information
?
-
-
no activity with recombinant GST-tagged EB1a protein. MPK6 is recruited to gamma-tubulin or gamma-tubulin complexes, but no direct phosphorylation of either gamma-tubulin or gamma-tubulin complex protein GCP4 wby MPK6 is detectable in vitro
-
-
-
additional information
?
-
no activity with recombinant GST-tagged EB1a protein. MPK6 is recruited to gamma-tubulin or gamma-tubulin complexes, but no direct phosphorylation of either gamma-tubulin or gamma-tubulin complex protein GCP4 wby MPK6 is detectable in vitro
-
-
-
additional information
?
-
-
enzyme is activated in response to a variety of cellular stresses and is involved in apoptosis in neurons
-
-
-
additional information
?
-
UNC-16 may regulate the localization of vesicular cargo by integrating JNK signaling and kinesin-1 transport
-
-
-
additional information
?
-
-
promoting influence of JNK-1 on both nuclear DAF-16 translocations and DAF-16 target gene sod-3, encoding superoxide dismutase 3, expressions within peripheral, non-neuronal tissue, JNK-1 modulates the intestinal stress-induced translocation of DAF-16 from the cytosol into the cell nucleus. JNK-1 is controlled by the MAPK JKK-1 under heat stress
-
-
-
additional information
?
-
promoting influence of JNK-1 on both nuclear DAF-16 translocations and DAF-16 target gene sod-3, encoding superoxide dismutase 3, expressions within peripheral, non-neuronal tissue, JNK-1 modulates the intestinal stress-induced translocation of DAF-16 from the cytosol into the cell nucleus. JNK-1 is controlled by the MAPK JKK-1 under heat stress
-
-
-
additional information
?
-
the mitogen-activated protein kinase homolog HOG1 gene controls glycerol accumulation in the pathogenic fungus Candida albicans
-
-
-
additional information
?
-
-
signaling pathways overview, the enzyme is important in transduction of external stimuli and signals from the cell membrane to nuclear and other intracellular targets, the enzyme is involved in regulation of several cellular processes in cell growth, differentiation, development cell cycle, death and survival, the enzyme is also involved in pathogenesis of several processes in the heart, e.g. hypertrophy, ischemic and reperfusion injury, as well as in cardioprotection, the MAPK family enzymes have regulatory function in the myocardium, overview
-
-
-
additional information
?
-
enzyme plays an important role in egg maturation or ectogenetic early development
-
-
-
additional information
?
-
enzyme plays an important role in egg maturation or ectogenetic early development
-
-
-
additional information
?
-
possible role of asymmetric p38 activation in zebrafish in symmetric and synchronous cleavage
-
-
-
additional information
?
-
possible role of asymmetric p38 activation in zebrafish in symmetric and synchronous cleavage
-
-
-
additional information
?
-
possible role of asymmetric p38 activation in zebrafish in symmetric and synchronous cleavage
-
-
-
additional information
?
-
-
spatiotemporal control of the Ras/ERK MAP kinase signaling pathway, involving multiple factors, is a key factor for determining the specificity of cellular responses including cell proliferation, cell differentiation, and cell survival, the fidelity of the signaling is regulated by docking interactions and by scaffolding, molecular mechanism of negative regulation of Ras/ERK signaling
-
-
-
additional information
?
-
-
ERK1 plays an essential role during the growth and differentiation
-
-
-
additional information
?
-
ERK1 plays an essential role during the growth and differentiation
-
-
-
additional information
?
-
-
JUN N-terminal kinase signaling is required to initiate the cell shape change at the onset of the epithelial wound healing. The embryonic JUN N-terminal kinase gene cassette is induced at the edge of the wound
-
-
-
additional information
?
-
-
functions of D-p38 is to attenuate antimicrobial peptide gene expression following exposure to lipopolysaccharide
-
-
-
additional information
?
-
-
DJNK signal transduction pathway mediates an immune response and morphogenesis
-
-
-
additional information
?
-
-
dorsal closure, a morphogenetic movement during Drosophila embryogenesis, is controlled by the Drosophila JNK pathway, D-Fos and the phosphatase Puckered
-
-
-
additional information
?
-
-
MAP kinase, ERK-A is required downstream of raf in the Sev signal transduction pathway
-
-
-
additional information
?
-
-
enzyme may function to modulate Dpp signaling
-
-
-
additional information
?
-
-
the JNK pathway is conserved and it is involved in controlling cell morphogenesis in Drosophila
-
-
-
additional information
?
-
-
during Drosophila embryogenesis, ectodermal cells of the lateral epithelium stretch in a coordinated fashion to internalize the amnioserosa cells and close the embryo dorsally. This process, dorsal closure, requires two signaling pathways: the Drosophila Jun-amino-terminal kinase pathway and the Dpp pathway
-
-
-
additional information
?
-
-
enzyme is part of mitogen-activated protein kinase pathways, crosstalk and regulation mechanism, overview
-
-
-
additional information
?
-
-
poor activity on free amino acids, consensus sequence of ERK2 is P-XS/TP, substrate specificity and recognition elements, e.g. PXTP, the activity on the protein substrate is much higher compared to a 14-residue peptide containing the phosphorylation site
-
-
-
additional information
?
-
-
Gpmk1 MAP kinase regulates the induction of secreted lipolytic enzymes
-
-
-
additional information
?
-
-
Gpmk1 MAP kinase regulates the induction of secreted lipolytic enzymes
-
-
-
additional information
?
-
-
ceramide activation of mitochondrial p38 mitogen-activated protein kinase is a potential mechanism for loss of mitochondrial transmembrane potential and apoptosis
-
-
-
additional information
?
-
-
p38 MAPK, ERK1, and ERK2 are involved in regulation of connective tissue growth factor, CTGF, in chondrocyte maturation and function, particularly in the hypertrophic zone, as part of the retinoid and BMP signaling pathways, overview, p38 MAPK stimulates CTGF expression, while ERK1 and ERK2 supress it
-
-
-
additional information
?
-
-
no phosphorylation of the activation domain of c-Jun
-
-
-
additional information
?
-
-
no phosphorylation of MAPK-activated protein kinase-2 and -3
-
-
-
additional information
?
-
enzyme is implicated in signal transduction pathways
-
-
-
additional information
?
-
-
BMK1 may regulate signaling events distinct from those controlled by the ERK group of enzymes
-
-
-
additional information
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the enzyme plays a crucial role in stress and inflammatory responses and is also involved in activation of the human immunodeficiency virus gene expression
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JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation, JNK1 activation may play an important role in tumor promotion
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enzyme is involved in the signal transduction pathway initiated by proinflammatory cytokines and UV radiation
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p493F12 gene maps to the human chromosome 21q21 region, a region that may be important in the pathogenesis of AD and Down's syndrome
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enzyme is activated by cellular stresses and plays an important role in regulating gene expression
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signaling pathway, including ERK, regulation, overview
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the enzyme is part of a signalling cascade resulting in an increase in Ca2+-fluxes, activation of NF-kappaB, and expression of interleukin-8, the cascade is stimulated by pathogens, e.g. Pseudomonas aeruginosa PAO1 and Staphylococcus aureus RN6390, binding to asialo-glycolipid receptors, e.g. the asialoGM1 receptor, in epithelial membranes, no activation occurs with the pil mutant of Pseudomonas aeruginosa and the agr mutant of Staphylococcus aureus RN6911, Ca2+-dependent signaling, overview
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interaction motifs of substrates are crucial for MAPK activity, motif Leu-Xaa-Leu preceded by 3-5 basic residues is abundant, docking mechanism in MAPK signalling, the recognition modules can function synergistically or competitively, MAPK determinants recognizing docking motifs, overview
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MAPKs play a pivotal role in signal transduction
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MAPKs, e.g. p38, play a key role in the transductin of biological signals from cell surface receptors, through the cytoplasm, to the transcriptional machinery in the nucleus
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p38 isozymes are involved in multiple cellular functions such as cell proliferation, cell differentiation, apoptosis, and inflammation response, p38 expression and activity in signaling in erythroid cells is independent of erythropoietin
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p38 MAP kinase mediates the activation of neutrophils and repression of TNF-alpha-induced apoptosis in response to inhibition by plasma opsonized crystals of calcium diphosphate dihydrate, p38 MAP kinase is involved in apoptosis of neutrophils, regulation overview
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signaling pathways overview, the enzyme is important in transduction of external stimuli and signals from the cell membrane to nuclear and other intracellular targets, the enzyme is involved in regulation of several cellular processes in cell growth, differentiation, development cell cycle, death and survival, the enzyme is also involved in pathogenesis of several processes in the heart, e.g. hypertrophy, ischemic and reperfusion injury, aas well as in cardioprotection, the MAPK family enzymes have regulatory function in the myocardium, overview
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the p38 MAPKalpha is involved in cell signal transduction and mediates responses to cell stresses and to growth factors
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arsenic trioxide induces apoptosis and mitogen-activated protein kinases in promyelocytes and cancer cells. It enhances adhesion, migration, phagocytosis, release, and activity of gelatinase and degranulation of secretory, specific, and gelatinase, but not azurophilic granules, and is dependent upon activation of p38 and/or JNK. Activation of p38 and JNK is not associated with the ability of arsenic trioxide to induce human neutrophil apoptosis, overview
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cadmium induces neuronal apoptosis in part through activation of Erk1, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of Erk1 pathway, mechanism, overview
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cadmium induces neuronal apoptosis in part through activation of Erk1, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of Erk1 pathway, mechanism, overview
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cadmium induces neuronal apoptosis in part through activation of Erk2, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of Erk2 pathway, mechanism, overview
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cadmium induces neuronal apoptosis in part through activation of Erk2, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of Erk2 pathway, mechanism, overview
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cadmium induces neuronal apoptosis in part through activation of JNK, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of JNK pathway, mechanism, overview
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cadmium induces neuronal apoptosis in part through activation of JNK, Cd-induced reactive oxygen species inhibit serine/threonine protein phosphatases 2A and 5, PP2A andPP5, leading to activation of JNK pathway, mechanism, overview
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JNK2 shows conformational flexibility in the MAP kinase insert and its involvement in the regulation of catalytic activity, the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners, overview
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p38 MAP kinase inhibitor SB203580 decreases TNF-alpha-mediated DNA binding activity of NF-?B, which is is involved in p38MAP kinase-mediated control of the MMP-9 gene in 5637 cells, overview
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p38 MAPK is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha
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Q16539
The mitogen-activated protein kinase p38 is a key regulator in the signaling pathways controlling the production of pro-inflammatory cytokines such as TNF-alpha and IL-1beta
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MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. The short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK. Comparison of the hydrophobic submotif in strong versus weak JNK-binding D-sites, overview. The D-sites of the JNK pathway activator MKK4 contains LXL, as do all three of the D-sites in activator MKK7 in the first 3 residues of the hydrophobic submotif. MKK D-sites that bind JNK weakly lack an extended hydrophobic motif
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p38beta can autophosphorylate and thus autoactivate itself, the C tail of p38beta inhibits autophosphorylation
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PMK1 is part of a highly conserved MAP kinase signal transduction pathway