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Information on EC 2.7.11.24 - mitogen-activated protein kinase and Organism(s) Mus musculus and UniProt Accession Q61532
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2.7.11.24 mitogen-activated protein kinaseIUBMB Comments
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 . 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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Word Map
- 2.7.11.24
- endothelial
- necrosis
- tnf
- agonist
- lipopolysaccharide
- 3-kinase
- pkc
- lps
- nf-kappab
- sirnas
- phosphatidylinositol
- caspase-3
- cardiac
- metastasis
-
lps-induced
- artery
- camp
- bcl-2
- monocyte
- chemokine
- collagen
- angiogenesis
- cox-2
- fibrosis
-
toll-like
- cyclins
-
neuroprotective
- melanoma
- stat3
- tnf-alpha
- prostaglandin
- c-fos
- phosphoinositide
- mtor
- cardiomyocytes
- factor-alpha
- osteoblast
-
dominant-negative
- creb
-
anti-apoptotic
- integrins
- cyclooxygenase-2
- angiotensin
- wortmannin
-
protein-coupled
- microglia
- mmp-9
- il-1beta
-
platelet-derived
- fak
- medicine
- drug development
- analysis
- pharmacology
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
mapk, p38, erk1/2, p38 mapk, mitogen-activated protein kinase, map kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, p38mapk, p38 map kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
c-Jun N-terminal kinase
cp38a
-
-
-
-
cp38b
-
-
-
-
CSAID binding protein
-
-
-
-
CSBP
-
-
-
-
Cytokine suppressive anti-inflammatory drug binding protein
-
-
-
-
ERK
ERK2
ERK5
-
-
-
-
JNK
JNK1
JNK2
MAP kinase
MAP kinase MXI2
-
-
-
-
MAP kinase p38 beta
-
-
-
-
MAP kinase p38 delta
-
-
-
-
MAP kinase p38 gamma
-
-
-
-
MAP kinase p38a
-
-
-
-
MAP kinase p38alpha
-
-
-
-
MAP kinase p38b
-
-
-
-
MAPK
mitogen-activated kinase
mitogen-activated protein kinase
-
-
-
-
mitogen-activated protein kinase 1
-
Mitogen-activated protein kinase p38 beta
-
-
-
-
Mitogen-activated protein kinase p38 delta
-
-
-
-
Mitogen-activated protein kinase p38 gamma
-
-
-
-
Mitogen-activated protein kinase p38a
-
-
-
-
Mitogen-activated protein kinase p38alpha
-
-
-
-
Mitogen-activated protein kinase p38b
-
-
-
-
p38
p38alpha MAP kinase
p38b
-
-
-
-
SAPK2A
-
-
-
-
stress-activated protein kinase 2a
-
-
-
-
additional information
MAPK
-
-
-
-
additional information
-
MAP kinase p38alpha is a member of the MAP kinase family
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
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
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
phospho group transfer
-
-
-
-
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.
CAS REGISTRY NUMBER
COMMENTARY
142243-02-5
-
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 + ATF2
ADP + phosphorylated ATF2
phosphorylation by p38 MAPK at threonine 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 + myelin basic protein
ADP + phosphorylated myelin basic protein
-
substrate of ERK2
-
-
?
ATP + Net
ADP + phosphorylated Net
an ETS family transcription factor
-
-
?
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 + 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
-
-
?
additional information
?
-
Jnk3-mediated signalling pathway is an important component in the pathogenesis of glutamate neurotoxicity
-
-
?
additional information
?
-
MKK4 is a JNK activator in vivo and an essential component of the JNK signal transduction pathway
-
-
?
additional information
?
-
JNK is necessary for T-cell differentiation but not for naive T-cell activation
-
-
?
additional information
?
-
-
JNK is necessary for T-cell differentiation but not for naive T-cell activation
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
-
ERK, but not p38 and JNK, is involved in TGF-beta production in macrophages, the phosphatidylserine-receptor is involved in the ERK signaling pathway, overview
-
-
?
additional information
?
-
-
regulation mechanism of p38 MAPK activity involving the protein kinases MKK3, MKK4, and MKK6, overview
-
-
?
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
?
-
-
measurement of ATPase activity of p38 MAPK in an NADH-coupled assay
-
-
?
additional information
?
-
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activation of JNK facilitates tumour necrosis factor-induced cell death. The p38 mitogen-activated protein kinase pathway is induced by TNF-stimulation, but it is not involved in TNF-induced cell death. p38alpha MAPK inhibits JNK activation and collaborates with IkappaB kinase 2 to prevent endotoxin-induced liver failure. p38alpha MAPK inhibits MKK4, and MKK3/6, regulation, overview
-
-
?
additional information
?
-
-
MAP kinases are essential signaling molecules that mediate many cellular effects of growth factors, cytokines, and stress stimuli
-
-
?
additional information
?
-
-
MAPKs are involved in the upstream regulation of inducible nitric oxide synthase, iNOS
-
-
?
additional information
?
-
-
p38 MAPK is induced in response to environmental stress, it is implicated in diverse cellular processes, including cell proliferation, differentiation, and survival of differentiated cells in the central nervous system, expression profile and roles of p38 MAPK in the developing brain, overview. Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse neural stem cells, overview
-
-
?
additional information
?
-
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
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 + activating transcription factor 2
ADP + phosphorylated activating transcription factor 2
-
ATF2
-
-
?
ATP + Elk-1
ADP + phosphorylated Elk-1
an ETS family transcription factor
-
-
?
ATP + Net
ADP + phosphorylated Net
an ETS family transcription factor
-
-
?
additional information
?
-
Jnk3-mediated signalling pathway is an important component in the pathogenesis of glutamate neurotoxicity
-
-
?
additional information
?
-
MKK4 is a JNK activator in vivo and an essential component of the JNK signal transduction pathway
-
-
?
additional information
?
-
JNK is necessary for T-cell differentiation but not for naive T-cell activation
-
-
?
additional information
?
-
-
JNK is necessary for T-cell differentiation but not for naive T-cell activation
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
-
the enzyme functions as a Scaffold factor in the JNK signaling pathway
-
-
?
additional information
?
-
-
ERK, but not p38 and JNK, is involved in TGF-beta production in macrophages, the phosphatidylserine-receptor is involved in the ERK signaling pathway, overview
-
-
?
additional information
?
-
-
regulation mechanism of p38 MAPK activity involving the protein kinases MKK3, MKK4, and MKK6, overview
-
-
?
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
?
-
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activated p39 MAPK inhibits steroid synthesis in adrenocortical Y1-BS1 cells, overview
-
-
?
additional information
?
-
activation of JNK facilitates tumour necrosis factor-induced cell death. The p38 mitogen-activated protein kinase pathway is induced by TNF-stimulation, but it is not involved in TNF-induced cell death. p38alpha MAPK inhibits JNK activation and collaborates with IkappaB kinase 2 to prevent endotoxin-induced liver failure. p38alpha MAPK inhibits MKK4, and MKK3/6, regulation, overview
-
-
?
additional information
?
-
-
MAP kinases are essential signaling molecules that mediate many cellular effects of growth factors, cytokines, and stress stimuli
-
-
?
additional information
?
-
-
MAPKs are involved in the upstream regulation of inducible nitric oxide synthase, iNOS
-
-
?
additional information
?
-
-
p38 MAPK is induced in response to environmental stress, it is implicated in diverse cellular processes, including cell proliferation, differentiation, and survival of differentiated cells in the central nervous system, expression profile and roles of p38 MAPK in the developing brain, overview. Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse neural stem cells, overview
-
-
?
additional information
?
-
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modeling, overview
-
-
?
additional information
?
-
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
additional information
?
-
trauma-hemorrhage suppresses MAPK phosphorylation and activation in lipopolysaccharide-unstimulated splenic dendritic cells, in lipopolysaccharide-unstimulated cells the activation is increased, modelling, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)acrylamide
-
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methanesulfinyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
-
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
-
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperazin-1-yl-3,4-dihydro-1H-quinazolin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 3.2 nM, the IC50 for mutants G110A and G110D are 37 nM and 56 nM, respectively, no inhibition of JNK3, JNK2, and ERK
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenyl)-7-piperidin-4-yl-3,4-dihydro-1H-quinolin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 0.74 nM, the IC50 for mutants G110A and G110D are 26 nM and 67 nM, respectively, no inhibition of JNK3, JNK2, and ERK
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
highly selective for p38 isozyme alpha wild-type with IC50 of 4.3 nM, the IC50 for mutants G110A and G110D are 61 nM and 160 nM, respectively, no inhibition of JNK3, JNK2, and ERK
2-(4-fluorophenyl)-N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(R)-phenylethyl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(S)-phenylethyl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine
-
4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(R)-3-methylbutan-2-yl]pyridin-2-amine
-
-
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(S)-3-methylbutan-2-yl]pyridin-2-amine
-
-
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1,2-dimethylpropyl)pyridin-2-amine
-
-
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
-
-
adenylyl-beta,gamma-methylene diphosphonic acid
-
i.e. AMP-PCP, MgAMP-PCP shows a mixed inhibition pattern in the kinase reaction, and a competitive pattern in the ATPase reaction
lignocaine
-
the enzyme inhibition by lignocine may involve voltage-sensitive sodium channels, the enzyme attenuates the induction of MAPK activation by lipopolysaccharides, overview
N-(1,2-dimethylpropyl)-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
-
-
N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)2-phenoxypropanamide
-
N-sec-butyl-4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-amine
-
N-sec-butyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
-
-
N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
-
skepinone-L
-
the specificity by which SCD-1 modulates the phospholipid composition and inhibits p38 MAPK signaling (among survival/stress pathways), thereby preventing endoplasmic reticulum stress (but not other SCD-1-dependent responses), suggests selective protein-lipid interactions
trans-4-([4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
-
-
trans-4-([4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
-
-
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
highly selective for p38 isozyme alpha wild-type and mutants with IC50 of 0.10-0.14 nM, IC50 for JNK2 is 680 nM, for JNK3 970 nM and for ERK 660 nM
SB202190
inhibitor of p38 MAPKalpha, little or no inhibition of p38 MAPK beta, gamma, and delta
SB203580
-
noncompetitive in the kinase reaction, competitive versus ATP in the ATPase reaction, no classical linear inhibition kinetics at concentrations below 100 nM
SB203580
-
specific inhibitor of p38alpha MAP kinase, interaction analysis with immobilized enzyme in a surface plasmon resonance study, binding structure from the cyrstal structure of the enzyme-inhibitor complex
SB203580
-
inhibits p38 MAP kinase in T cells, administration of the pharmacological inhibitor of the kinase during the course of infection with the spirochete Borrelia burgdorferi results in reduced levels of IFN-gamma in the sera of infected mice
SB203580
inhibitor of p38 MAPKalpha, little or no inhibition of p38 MAPK beta, gamma, and delta
SP600125
-
SP600125 inhibits lipopolysaccharide- and lipoteichoic acid-induced iNOS/NO production by reducing lipopolysaccharide- and lipoteichoic acid-induced JNK protein phosphorylation
additional information
-
PD98059 and U0126 inhibit EGF-induced phosphorylation of Smad3
-
additional information
structural basis for inhibitor selectivity for p38 over other MAPKs such as ERK or JNK, overview
-
additional information
-
downregulation of MAP kinase activity can be initiated by dephosphorylation through multiple serine/threonine phosphatases, tyrosine-specific phosphatases, and dual specificity phosphatases, i.e. MAP kinase phosphatases, leading to the formation of monophosphorylated MAP kinases
-
additional information
-
PD98059 inhibits the activation of ERK1/2 with a IC50 value of 0.002 mM
-
additional information
PD98059 inhibits the activation of ERK1/2 with a IC50 value of 0.002 mM
-
additional information
PD98059 inhibits the activation of ERK1/2 with a IC50 value of 0.002 mM
-
additional information
PD98059 inhibits the activation of ERK1/2 with a IC50 value of 0.002 mM
-
additional information
-
some monounsaturated fatty acids inhibit p38 MAPK via selective protein-lipid interactions
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TNF-alpha
-
activates p38 MAPK mediated by protein kinases MKK3, MKK4, and MKK6, overview
-
additional information
-
inhibition of the phosphatidylserine-receptor activates ERK and TGF-beta production in vivo
-
additional information
-
MAPKs are activated by phosphorxylation through MEK/MAPK kinases
-
additional information
-
mechanism of p38 MAP kinase activation in vivo, coordinated and selective actions of protein kinases MKK3, MKK4, and MKK6 in response to cytokines and exposure to environmental stress are part of the regulation, overview
-
additional information
-
the recombinant detagged enzyme is activated by specific phosphorylation at Thr180 and Tyr182 through recombinant GST-tagged MKK6 mutant S207E/T211E
-
additional information
-
full activation of the MAP kinases requires dual phosphorylation of the Thr and Tyr residues in the TXY motif of the activation loop by MAP kinase kinases, p38alpha phosphorylated at both Thr180 and Tyr182 is 10-20fold more active than p38alpha phosphorylated at Thr180 only, p38alpha phosphorylation by MKK6
-
additional information
-
H2O2 and 4-hydroxy-2-nonenal increase phosphorylation and activation of p38 MAPK, but not of ERK1/2
-
additional information
H2O2 and 4-hydroxy-2-nonenal increase phosphorylation and activation of p38 MAPK, but not of ERK1/2
-
additional information
H2O2 and 4-hydroxy-2-nonenal increase phosphorylation and activation of p38 MAPK, but not of ERK1/2
-
additional information
-
lipolysaccharide induces the MAPK activation, which is inhibited by lignocaine in case of ERK and p38, but not of JNK, overview
-
additional information
-
MAPKs are activated by phosphorylation through MAPK kinases
-
additional information
MAPKs are activated by phosphorylation through MAPK kinases
-
additional information
MAPKs are activated by phosphorylation through MAPK kinases
-
additional information
MAPKs are activated by phosphorylation through MAPK kinases
-
additional information
MAPKs are activated by phosphorylation through MAPK kinases, overview. TNF induces p38 MAP kinase, JNK is induced by TNF and lipopolysaccharide
-
additional information
no activation JNK1 by H2O2 and 4-hydroxy-2-nonenal
-
additional information
no activation JNK1 by H2O2 and 4-hydroxy-2-nonenal
-
additional information
no activation JNK2 by H2O2 and 4-hydroxy-2-nonenal
-
additional information
no activation JNK2 by H2O2 and 4-hydroxy-2-nonenal
-
additional information
-
activated by infection or cellular stressors such as mechanical wear, heat, or osmotic shock
-
additional information
-
p38 MAPK is activated by phosphorylation. Inhibition of SCD-1 decreases the proportion of monounsaturated fatty acid-containing phospholipids and activates p38 MAPK
-
additional information
the ERK2 MAPK is activated by phosphorylation through MEK1 and MEK2
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state kinetics, kinetic mechanism for p38 MAP kinase alpha kinase and ATPase activities, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000021
SB203580
-
ATPase reaction versus ATP, pH 7.6, 27°C, recombinant p38 MAPK
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00252
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus
-
0.000041
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methanesulfinyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus
-
0.000019
(E)-3-(2,4-dimethoxyphenyl)-N-(4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]pyridin-2-yl)acrylamide
Mus musculus
-
0.0000043 - 0.00016
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
0.000333
2-(4-fluorophenyl)-3-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus
-
-
0.00156
2-(4-fluorophenyl)-N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
Mus musculus
-
0.000038
3-(4-fluorophenyl)-2-(2-isopropylaminopyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus
-
-
0.00045
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(R)-phenylethyl)pyridin-2-amine
Mus musculus
-
0.000006
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(1(S)-phenylethyl)pyridin-2-amine
Mus musculus
-
0.00006
4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]-N-(tetrahydro-2H-pyran-4-yl)pyridin-2-amine
Mus musculus
-
0.000238
4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
Mus musculus
-
-
0.00072
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-phenylethyl)pyridin-2-amine
Mus musculus
-
-
0.000794
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-(3-methylbutan-2-yl)pyridin-2-amine
Mus musculus
-
-
0.00479
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1R)-1-phenylethyl]pyridin-2-amine
Mus musculus
-
-
0.000431
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(1S)-1-phenylethyl]pyridin-2-amine
Mus musculus
-
-
0.00159
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(R)-3-methylbutan-2-yl]pyridin-2-amine
Mus musculus
-
-
0.00576
4-[3-(4-fluorophenyl)quinoxalin-2-yl]-N-[(S)-3-methylbutan-2-yl]pyridin-2-amine
Mus musculus
-
-
0.000211
4-[4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-ylamine]-cyclohexanol
Mus musculus
-
-
0.00946
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1,2-dimethylpropyl)pyridin-2-amine
Mus musculus
-
-
0.000412
4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]-N-(1-methylethyl)pyridin-2-amine
Mus musculus
-
-
0.00138
N-(1,2-dimethylpropyl)-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus
-
-
0.00089
N-(4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-yl)2-phenoxypropanamide
Mus musculus
-
0.00153
N-benzyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus
-
-
0.00003
N-sec-butyl-4-[3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl]pyridin-2-amine
Mus musculus
-
0.000595
N-sec-butyl-4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-amine
Mus musculus
-
-
0.000522
N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
Mus musculus
-
mixture of N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine and N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
0.000522
N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine
Mus musculus
-
mixture of N-tert-butyl-4-[3-(4-fluorophenyl)pyrido[3,4-b]pyrazin-2-yl]pyridin-2-amine and N-tert-butyl-4-[2-(4-fluorophenyl)pyrido[3,4-b]pyrazin-3-yl]pyridin-2-amine
0.0003
N-[4-(3-(4-fluorophenyl)-5-isopropylisoxazol-4-yl)pyridin-2-yl]acetamide
Mus musculus
-
0.000015 - 0.000048
pyridinyl imidazole-type inhibitors
Mus musculus
IC50 of 15-48 nM
-
0.000259
trans-4-([4-[3-(4-fluorophenyl)-6,7-dimethylquinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
Mus musculus
-
-
0.000608
trans-4-([4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-yl]amino)cyclohexanol
Mus musculus
-
-
0.0000001 - 0.00097
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
0.0000043
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
Mus musculus
highly selective for p38 isozyme alpha wild-type with IC50 of 4.3 nM, respectively, no inhibition of JNK3, JNK2, and ERK
0.000061
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
Mus musculus
IC50 for mutant G110A 61 nM
0.00016
1-(2,6-dichloro-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-7-(1,2,3,6-tetrahydro-pyridin-4-yl)-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one
Mus musculus
IC50 mutant G110D 160 nM, respectively, no inhibition of JNK3, JNK2, and ERK
0.0000001 - 0.00000014
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
Mus musculus
highly selective for p38 isozyme alpha wild-type and mutants with IC50 of 0.10-0.14 nM
0.00066
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
Mus musculus
Ic50 for ERK 660 nM
0.00068
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
Mus musculus
IC50 for JNK2 is 680 nM
0.00097
[4-[3-methyl-2-piperidin-4-yl-5-(3-trifluoromethyl-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-yl]-((S)-1-phenyl-ethyl)-amine
Mus musculus
IC50 for JNK3 970 nM
additional information
2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[2,3-b]pyrazine
Mus musculus
-
46% at 10 microM
additional information
2-(4-fluorophenyl)-3-pyridin-4-ylpyrido[3,4-b]pyrazine
Mus musculus
-
33% at 10 microM, mixture of 3-(4-fluorophenyl)-2-pyridin-4-ylpyrido[3,4-b]pyrazine and 2-(4-fluorophenyl)-3-pyridin-4-ylpyrido[3,4-b]pyrazine
additional information
2-(4-fluorophenyl)-6-methoxy-3-(pyridin-4-yl)quinoxaline
Mus musculus
-
33% at 10 microM
additional information
3-(4-fluorophenyl)-2-pyridin-4-ylpyrido[3,4-b]pyrazine
Mus musculus
-
33% at 10 microM, mixture of 3-(4-fluorophenyl)-2-pyridin-4-ylpyrido[3,4-b]pyrazine and 2-(4-fluorophenyl)-3-pyridin-4-ylpyrido[3,4-b]pyrazine
additional information
6,7-dichloro-2-(4-fluorophenyl)-3-pyridin-4-ylquinoxaline
Mus musculus
-
39% at 10 microM
additional information
N-benzyl-4-[3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
Mus musculus
-
9% at 10 microM
additional information
N-benzyl-4-[6,7-dichloro-3-(4-fluorophenyl)quinoxalin-2-yl]pyridin-2-amine
Mus musculus
-
37% at 10 microM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
additional information
-
using a relatively low induction temperature (21°C in comparison to 32°C) phosphorylation is almost completely prevented. Combining a short 5 h induction with a low expression temperature (21°C) results in highly homogeneous unphosphorylated protein
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
p38 MAPK is expressed predominantly in nestin-positive cells in the cerebral cortex in embryonic day 10 brain
-
p38 MAPK is expressed predominantly in nestin-positive cells in the cerebral cortex in embryonic day 10 brain, the expression of the protein decreases gradually during development
-
primary cultures prepared from embryonic mouse brains, i.e. cerebral hemisphere and thalamus
adrenocortical cell line, predominant expression of isozyme p38 MAPKalpha
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
additional information
metabolism
-
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
MAPK cascade proteins bind to each other selectively via docking interactions
physiological function
-
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
-
the JNKs signal transduction pathway plays an important role in coordinating cellular responses including apoptosis, proliferation, and neoplastic transformation
physiological function
-
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
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
-
p38 MAPK might show selective protein-lipid interactions
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MK06_MOUSE
720
0
82199
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
activity requires phosphorylation of both Tyr and Thr residues, the two phosphorylation sites are separated by only a single residue
phosphoprotein
-
native and recombinant p38 MAPKalpha is activated by phosphorylation at Thr180 and Tyr182 through recombinant GST-tagged MKK6b mutant S207E/T211E, for activation and specific dual phosphorylation of the recombinant enzyme
phosphoprotein
-
p38alpha MAP kinase is phosphorylated by the MAPKK MKK6, EC 2.7.11.25, at Thr180 and Tyr182, phosphorylation activates p38alpha MAPK
phosphoprotein
-
the MAPKs are activated by phosphorylation through MAPK kinases, overview
phosphoprotein
-
full activation of the MAP kinases requires dual phosphorylation of the Thr and Tyr residues in the TXY motif of the activation loop by MAP kinase kinases. Dephosphorylation of MAP kinases by phosphatases, e.g. multiple serine/threonine phosphatases, tyrosine-specific phosphatases, and dual specificity phosphatases, leads to formation of monophosphorylated enzymes and inhibition of the MAP kinases. p38alpha phosphorylated at both Thr180 and Tyr182 is 10-20fold more active than p38alpha phosphorylated at Thr180 only, whereas p38alpha phosphorylated at Tyr182 alone is inactive, the dual-specific MKP5, the tyrosine-specific hematopoietic protein-tyrosine phosphatase, and the serine/threonine-specific PP2Calpha are all highly specific for the dephosphorylation of p38alpha, p38alpha phosphorylation by MKK6, kinetics, overview
phosphoprotein
JNK is activated by phosphorylation at Thr183 and Tyr185 through MKKs
phosphoprotein
MAPKs are activated by phosphorylation through MAPK kinases
phosphoprotein
p38 and ERK1/2 are activated by phosphorylation at Thr180 and Tyr182, or Thr202 and Tyr204, respectively, through MKKs
phosphoprotein
p38alpha MAPK are activated by phosphorylation through MAPK kinases, e.g. MKK3 and MKK6, overview
phosphoprotein
MKKs efficiently phosphorylate their cognate, within-pathway MAPKs and do not appreciably phosphorylate MAPKs in other pathways. The ERK MAPK is activated by phosphorylation through MEK1 and MEK2
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
p38alpha active mutants crystallized by sitting-drop vapour-diffusion method, mutant D176A/F327L to 1.45 A resolution, crystals of the three p38alpha mutants belong to the orthorhombic space group P212121, with one molecule in the asymmetric unit
-
purified p38 isozyme alpha bound to several inhibitors pyridinyl imidazole-type inhibitors, X-ray diffraction structure determination and analysis at 2.1-2.5 A resolution
purified recombinant p38alpha MAP kinase free or in complex with inhibitor SB203580, sitting or hanging drop vapour diffusion method at 16-20°C, 16 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 100 mM NaCl, 10 mM MgCl2, 10 mM DTT, and 5% glycerol is mixed with reservoir solution containing 10-20% PEG 4000, 18% ethylene glycol, 0.1 M cacodylic acid, pH 6.0, at a volume ratio of 3:2, X-ray diffraction structure determination and analysis at 1.9-2.7 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D176A
-
active p38alpha mutant, crystals do not appear spontaneously, cross-seeding approaches using crystals of mutant D176A+F327L as the source of microseeds results in crystals suitable for X-ray analysis
D176A/F327L
-
most active p38alpha mutant, improvement of crystallization assays, obtained with abolishing phosphorylation completely by reducing both the temperature and duration of induction and by significantly shortening the N-terminal hexahistidine spacer, facilitating the growth of well diffracting crystals
D176A/F327S
-
active p38alpha mutant, crystals do not appear spontaneously, cross-seeding approaches using crystals of mutant D176A+F327L as the source of microseeds results in crystals suitable for X-ray analysis
G110A
site-directed mutagenesis of isozyme alpha, the mutant shows a slightly decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme
G110D
site-directed mutagenesis of isozyme alpha, the mutant shows a decreased Km value for ATP, but unaltered activity compared to the wild-type enzyme, decreased sensitivity for inhibitors compared to the wild-type enzyme
additional information
additional information
-
enzyme-deficient mutant mice show defects in growth arrest and increased tumorigenesis
additional information
-
transgenic mice expressing a dominant negative mutant MAP kinase, inhibits the activity of endogenous p38 MAP kinase and reduces levels of IFN-gamma in serum
additional information
construction of mutant knockout p38alphaLPC-KO mice, hepatocyte-specific ablation of p38alpha in mice results in activation of MKK4 and MKK3/6 and excessive activation of JNK in the liver after in vivo challenge with bacterial lipopolysaccharide. Despite increased JNK activity, p38alpha-deficient hepatocytes are not sensitive to LPS/TNF toxicity showing that JNK activation is not sufficient to mediate TNF-induced liver damage. Lipopolysaccharide injection causes liver failure in mice lacking both p38alpha and IkappaB kinase 2 in hepatocytes, when combined with partial nuclear factor-kappaB inhibition, p38alpha deficiency sensitizes the liver to cytokine-induced damage
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 100 mM NaCl, 50 mM Tris-HCl buffer, pH 7.4, 10 mM DTT, 10 mM MgCl2, 5% glycerol
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged p38 isozyme alpha from Escherichia coli strain BL21(DE3) by two steps of ion exchange chromatography to homogeneity, the recombinant enzyme is detagged
-
recombinant His-tagged p38alpha from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography to homogeneity
-
recombinant His-tagged p38alpha MAP kinase from Escherichia coli strain BL21(DE3) by nickel chelate affinity chromatohgraphy, dialysis, and ion exchange chromatography to homogeneity, the His-tag is cleaved off by thrombin
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of GST-tagged p38 isozyme alpha in Escherichia coli strain BL21(DE3)
-
p38alpha active mutants subcloned into vector pET-28a and expressed in Rosetta strain of Escherichia coli
-
p38alpha MAP kinase expression in Escherichia coli strain BL21(DE3) as His-tagged protein with a thrombin cleavage site
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pharmacology
-
MAPKs are targets for inhibitors and pharmacological drug development
medicine
-
role in immune response to the spirochete of Borrelia burgdorferi mediated by CD4+ T cells, p38 MAP kinase pathway mediates production of IFN-gamma in response to a specific antigen, IL-12 contributes to IFN-gamma production by Borrelia burgdorferi specific effector Th1 cells
medicine
-
inhibition of p38 alpha mitogen-activated protein kinase is a promising therapeutic strategy for the treatment of cytokine-driven disorders like inflammatory bowel disease or rheumatoid arthritis
medicine
-
small-molecule inhibitors of JNK1 activity might be developed as therapeutics against diabetes
medicine
-
targeting JNK inhibition in the CNS may prove to protect against neurodegenerative insults, by either inhibiting JNK activation in neurons associated with increased apoptosis or preventing the inflammatory response in glial cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ershler, M.; Nagorskaya, T.V.; Visser, J.W.; Belyavsky, A.V.
Novel CDC2-related protein kinases produced in murine hematopoietic stem cells
Gene
124
305-306
1993
Mus musculus (P47811), Mus musculus (P63085), Mus musculus (Q61532)
Canagarajah, B.J.; Khokhlatchev, A.; Cobb, M.H.; Goldsmith, E.J.
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
Cell
90
859-869
1997
Mus musculus (P63085)
Zhang, F.; Strand, A.; Robbins, D.; Cobb, M.H.; Goldsmith, E.J.
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
Nature
367
704-711
1994
Mus musculus (P63085)
Payne, D.M.; Rossomando, A.J.; Martino, P.; Erickson, A.K.; Her, J.H.; Shabanowitz, J.; Hunt, D.F.; Weber, M.J.; Sturgill, T.W.
Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase)
EMBO J.
10
885-892
1991
Mus musculus (P63085)
Her, J.H.; Wu, J.; Rall, T.B.; Sturgill, T.W.; Weber, M.J.
Sequence of pp42/MAP kinase, a serine/threonine kinase regulated by tyrosine phosphorylation
Nucleic Acids Res.
19
3743
1991
Mus musculus (P63085)
Boulton, T.G.; Nye, S.H.; Robbins, D.J.; Ip, N.Y.; Radziejewska, E.; Morgenbesser, S.D.; DePinho, R.A.; Panayotatos, N.; Cobb, M.H.; Yancopoulos, G.D.
ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF
Cell
65
663-675
1991
Rattus norvegicus (P27704), Mus musculus (P63085)
Derijard, B.; Raingeaud, J.; Barrett, T.; Wu, I.H.; Han, J.; Ulevitch, R.J.; Davis, R.J.
Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms
Science
267
682-685
1995
Homo sapiens (P45983), Homo sapiens, Mus musculus (P47811)
Wang, Z.; Harkins, P.C.; Ulevitch, R.J.; Han, J.; Cobb, M.H.; Goldsmith, E.J.
The structure of mitogen-activated protein kinase p38 at 2.1-A resolution
Proc. Natl. Acad. Sci. USA
94
2327-2332
1997
Mus musculus (P47811)
Han, J.; Lee, J.D.; Bibbs, L.; Ulevitch, R.J.
A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells
Science
265
808-811
1994
Mus musculus (P47811)
Turgeon, B.; Saba-El-Leil, M.K.; Meloche, S.
Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa
Biochem. J.
346
169-175
2000
Mus musculus (Q61532)
-
Ito, M.; Yoshioka, K.; Akechi, M.; Yamashita, S.; Takamatsu, N.; Sugiyama, K.; Hibi, M.; Nakabeppu, Y.; Shiba, T.; Yamamoto, K.I.
JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
Mol. Cell. Biol.
19
7539-7548
1999
Mus musculus (Q61831), Mus musculus (Q91Y86), Mus musculus (Q9WTU6), Mus musculus
Yang, D.D.; Kuan, C.Y.; Whitmarsh, A.J.; Rincon, M.; Zheng, T.S.; Davis, R.J.; Rakic, P.; Flavell, R.A.
Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene
Nature
389
865-870
1997
Mus musculus (Q61831)
Martin, J.H.; Mohit, A.A.; Miller, C.A.
Developmental expression in the mouse nervous system of the p493F12 SAP kinase
Brain Res. Mol. Brain Res.
35
47-57
1996
Mus musculus (Q61831), Mus musculus
Whitmarsh, A.J.; Kuan, C.Y.; Kennedy, N.J.; Kelkar, N.; Haydar, T.F.; Mordes, J.P.; Appel, M.; Rossini, A.A.; Jones, S.N.; Flavell, R.A.; Rakic, P.; Davis, R.J.
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Genes Dev.
15
2421-2432
2001
Mus musculus (Q91Y86)
Dong, C.; Yang, D.D.; Tournier, C.; Whitmarsh, A.J.; Xu, J.; Davis, R.J.; Flavell, R.A.
JNK is required for effector T-cell function but not for T-cell activation
Nature
405
91-94
2000
Mus musculus (Q91Y86), Mus musculus
Yang, D.; Tournier, C.; Wysk, M.; Lu, H.T.; Xu, J.; Davis, R.J.; Flavell, R.A.
Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity
Proc. Natl. Acad. Sci. USA
94
3004-3009
1997
Mus musculus (Q91Y86)
Tournier, C.; Whitmarsh, A.J.; Cavanagh, J.; Barrett, T.; Davis, R.J.
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase
Proc. Natl. Acad. Sci. USA
94
7337-7342
1997
Mus musculus (Q91Y86)
Bain, J.; McLauchlan, H.; Elliott, M.; Cohen, P.
The specificities of protein kinase inhibitors: an update
Biochem. J.
371
199-204
2003
Homo sapiens, Mus musculus
Matsuura, I.; Wang, G.; He, D.; Liu, F.
Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3
Biochemistry
44
12546-12553
2005
Mus musculus
Otsuka, M.; Goto, K.; Tsuchiya, S.; Aramaki, Y.
Phosphatidylserine-specific receptor contributes to TGF-beta production in macrophages through a MAP kinase, ERK
Biol. Pharm. Bull.
28
1707-1710
2005
Mus musculus
Szafranska, A.E.; Dalby, K.N.
Kinetic mechanism for p38 MAP kinase alpha. A partial rapid-equilibrium random-order ternary-complex mechanism for the phosphorylation of a protein substrate
FEBS J.
272
4631-4645
2005
Mus musculus
Brancho, D.; Tanaka, N.; Jaeschke, A.; Ventura, J.J.; Kelkar, N.; Tanaka, Y.; Kyuuma, M.; Takeshita, T.; Flavell, R.A.; Davis, R.J.
Mechanism of p38 MAP kinase activation in vivo
Genes Dev.
17
1969-1978
2003
Mus musculus
Ravingerova, T.; Barancik, M.; Strniskova, M.
Mitogen-activated protein kinases: a new therapeutic target in cardiac pathology
Mol. Cell. Biochem.
247
127-138
2003
Canis lupus familiaris, Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Fitzgerald, C.E.; Patel, S.B.; Becker, J.W.; Cameron, P.M.; Zaller, D.; Pikounis, V.B.; O'Keefe, S.J.; Scapin, G.
Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity
Nat. Struct. Biol.
10
764-769
2003
Mus musculus (P47811)
Bukhtiyarova, M.; Northrop, K.; Chai, X.; Casper, D.; Karpusas, M.; Springman, E.
Improved expression, purification, and crystallization of p38alpha MAP kinase
Protein Expr. Purif.
37
154-161
2004
Mus musculus
Diskin, R.; Engelberg, D.; Livnah, O.
High-resolution diffracting crystals of intrinsically active p38alpha MAP kinase: a case study for low-throughput approaches
Acta Crystallogr. Sect. D
63
260-265
2007
Mus musculus
Hedrick, M.N.; Olson, C.M.; Conze, D.B.; Bates, T.C.; Rincon, M.; Anguita, J.
Control of Borrelia burgdorferi-specific CD4+-T-cell effector function by interleukin-12- and T-cell receptor-induced p38 mitogen-activated protein kinase activity
Infect. Immun.
74
5713-5717
2006
Mus musculus, Mus musculus C3H/HEN
Kawasaki, T.; Choudhry, M.A.; Schwacha, M.G.; Fujimi, S.; Lederer, J.A.; Bland, K.I.; Chaudry, I.H.
Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process
Am. J. Physiol. Cell Physiol.
294
C754-C764
2008
Mus musculus, Mus musculus (Q61831), Mus musculus (Q91Y86), Mus musculus (Q9WTU6)
Lee, P.Y.; Tsai, P.S.; Huang, Y.H.; Huang, C.J.
Inhibition of toll-like receptor-4, nuclear factor-kappaB and mitogen-activated protein kinase by lignocaine may involve voltage-sensitive sodium channels
Clin. Exp. Pharmacol. Physiol.
35
1052-1058
2008
Mus musculus
Heinrichsdorff, J.; Luedde, T.; Perdiguero, E.; Nebreda, A.R.; Pasparakis, M.
p38alpha MAPK inhibits JNK activation and collaborates with IkappaB kinase 2 to prevent endotoxin-induced liver failure
EMBO Rep.
9
1048-1054
2008
Mus musculus (P47811), Mus musculus C57BL/6 (P47811)
Zhang, Y.Y.; Mei, Z.Q.; Wu, J.W.; Wang, Z.X.
Enzymatic activity and substrate specificity of mitogen-activated protein kinase p38alpha in different phosphorylation states
J. Biol. Chem.
283
26591-26601
2008
Mus musculus
Abidi, P.; Zhang, H.; Zaidi, S.M.; Shen, W.J.; Leers-Sucheta, S.; Cortez, Y.; Han, J.; Azhar, S.
Oxidative stress-induced inhibition of adrenal steroidogenesis requires participation of p38 mitogen-activated protein kinase signaling pathway
J. Endocrinol.
198
193-207
2008
Mus musculus, Mus musculus (Q91Y86), Mus musculus (Q9WTU6)
Sato, K.; Hamanoue, M.; Takamatsu, K.
Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse neural stem cells
J. Neurosci. Res.
86
2179-2189
2008
Mus musculus
Pocivavsek, A.; Rebeck, G.W.
Inhibition of c-Jun N-terminal kinase increases apoE expression in vitro and in vivo
Biochem. Biophys. Res. Commun.
387
516-520
2009
Mus musculus
Beck, I.M.; Berghe, W.V.; Gerlo, S.; Bougarne, N.; Vermeulen, L.; De Bosscher, K.; Haegeman, G.
Glucocorticoids and mitogen- and stress-activated protein kinase 1 inhibitors: possible partners in the combat against inflammation
Biochem. Pharmacol.
77
1194-1205
2009
Mus musculus
Lin, H.Y.; Shen, S.C.; Lin, C.W.; Wu, M.S.; Chen, Y.C.
Cobalt protoporphyrin inhibition of lipopolysaccharide or lipoteichoic acid-induced nitric oxide production via blocking c-Jun N-terminal kinase activation and nitric oxide enzyme activity
Chem. Biol. Interact.
180
202-210
2009
Mus musculus
Yao, K.; Cho, Y.Y.; Bode, A.M.; Vummenthala, A.; Park, J.G.; Liu, K.; Pang, Y.P.; Dong, Z.
A selective small-molecule inhibitor of c-Jun N-terminal kinase 1
FEBS Lett.
583
2208-2212
2009
Mus musculus, Homo sapiens (P45983)
Peifer, C.; Abadleh, M.; Bischof, J.; Hauser, D.; Schattel, V.; Hirner, H.; Knippschild, U.; Laufer, S.
3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta
J. Med. Chem.
52
7618-7630
2009
Mus musculus (P47811)
Koch, P.; Jahns, H.; Schattel, V.; Goettert, M.; Laufer, S.
Pyridinylquinoxalines and pyridinylpyridopyrazines as lead compounds for novel p38 alpha mitogen-activated protein kinase inhibitors
J. Med. Chem.
53
1128-1137
2010
Mus musculus
Koeberle, A.; Pergola, C.; Shindou, H.; Koeberle, S.C.; Shimizu, T.; Laufer, S.A.; Werz, O.
Role of p38 mitogen-activated protein kinase in linking stearoyl-CoA desaturase-1 activity with endoplasmic reticulum homeostasis
FASEB J.
29
2439-2449
2015
Mus musculus
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