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ATP + protein
ADP + phosphoprotein
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + ASK1
ADP + phosphorylated ASK1
ASK2 activates ASK1 by direct phosphorylation
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + ERK
ADP + phosphorylated ERK
ATP + ERK5
ADP + phosphorylated ERK5
-
-
-
-
?
ATP + GSK3beta
ADP + phosphorylated GSK3beta
-
regulates phosphorylation at serine 9
-
-
?
ATP + JNK
ADP + phosphorylated JNK
ATP + MEK
ADP + phosphorylated MEK
ATP + MEK1
ADP + phosphorylated MEK1
ATP + MEK5
ADP + phosphorylated MEK5
ATP + MKK
ADP + phosphorylated MKK
ATP + MKK1
ADP + phosphorylated MKK1
ATP + MKK3
ADP + phosphorylated MKK3
ATP + MKK4
ADP + phosphorylated MKK4
ATP + MKK6
ADP + phosphorylated MKK6
ATP + MKK7
ADP + phosphorylated MKK7
ATP + p38
ADP + phosphorylated p38
-
ASK1, TAK1
-
-
?
ATP + protein
ADP + phosphoprotein
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + Ror2
ADP + phospho-Ror2
BAD + ATP
BAD-phosphate + ADP
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
additional information
?
-
ATP + ERK
ADP + phosphorylated ERK
-
-
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
TPL-2, TAK1, MEKK3
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
-
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
ASK1, TPL-2, TAK1, MLK3, MEKK3
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
required for Wnt-mediated JNK activation in B cells
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
-
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
MEK1 activates the ERK2 signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
substrate is a MAPKK
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
-
a MAPKK
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
-
activated MEK5 activates ERK5
-
-
?
ATP + MKK
ADP + phosphorylated MKK
-
a MAPKK
-
-
?
ATP + MKK
ADP + phosphorylated MKK
-
induction of the JNK pathway activation
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
a MAPKK, recombinant GST-tagged MKK1
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
-
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
a MAPKK
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
ASK1
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
-
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
MKK4 activates the JNK signaling pathway
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK, activity of wild-type and mutant MEKK1 with wild-type and mutant MKK4, determination of the MKK4 binding site of MEKK1, overview
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK, recombinant GST-tagged MKK4
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
i.e. SEK1, a MAPKK
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
substrate is a MAPKK
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
ASK1
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
-
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
a MAPKK
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
ASK1, TAK1
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
a MAPKK
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TAK1 phosphorylates Ror2, a receptor tyrosine kinase, at multiple sites, activity of TAK1 with Ror2 phosphorylation site mutants, overview
-
-
?
additional information
?
-
MEKK4 binds to Cdc42 and Rac
-
-
?
additional information
?
-
-
MEKK4 binds to Cdc42 and Rac
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21Waf1/Cip1-mediated growth arrest
-
-
?
additional information
?
-
-
MEKK2 and MEKK3 are involved in activation of signal transduction pathways via toll-like receptor TLR, mitogen-activated protein kinases MAPK, and NF-kappaB, overview
-
-
?
additional information
?
-
-
MEKK2 induces the JNK signaling pathway, overview
-
-
?
additional information
?
-
-
the enzyme is part of the MAPK signaling cascades, overview
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, overview, MEKK1 regulates calpain-dependent cell migration via regulation of th ERK2-dependent signaling pathway and binding to focal adhesions, actinin, and FAK, overview
-
-
?
additional information
?
-
-
the enzyme docks at the DVD docking site of MAPKK, a stretch of about 20 amino acids immediately on the C-terminal side of the catalytic domain, MAPKK with mutated DVD docking sites are inhibitory for the MAPKKK
-
-
?
additional information
?
-
-
endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress
-
-
?
additional information
?
-
-
MEKK3 is required for IL-1R and LPS-induced IL-6 production in fibroblasts
-
-
?
additional information
?
-
-
MEKK4 is a signaling protein of the p38 MAPK pathway
-
-
?
additional information
?
-
-
induces activation of NF-kappaB reporter activity, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
involved in the activation of NF-kappaB, negatively regulates MEKK3-induced activation of NF-kappaB reporter activity, able to autophosphorylate at multiple sites when bound to TAB1, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK and JNK pathways in cells of the imune system in response to inflammatory mediators, knockout mice show normal development but defects in inflammatory response, involved in T-cell proliferation, probably involved in cardiac myocyte differentiation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK1/2 and possibly also ERK3, important function in vascular development, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK and p38MAP kinases in response to stress stimuli, knockout mice usually dying shortly after birth due to neural tube and skeletal malformations, functions in regulation of apoptosis and cell migration, possibly acts as central regulator of calcium-mediated signaling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK during neuronal migration in cerebal cortex development
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates the p38 pathway in response to stress and DNA damage
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, appears to transduce signals for JNK and ERK1/2 activation by pro-inflammatory stimuli and growth factors, key regulator of cell migration, deletion mutants are viable and fertile but display altered migration of epithelial cells resulting in defective eyelid closure, enzyme interacts directly with MEK1, MEK2 and c-Raf, involved in oxidative stress induced apoptosis in cardiac myocytes, enzyme deficiency individuals have diminished B-cell numbers, directly and indirectly involved in cell migration
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, important for the transduction of survival signals, involved in the regulation of apoptosis, important for TGFbeta signalling, deletion mutation in adult mice results in bone marrow and liver failure due to increased apoptosis of hematopoetic cells and hepatocytes, embryonic deletion is lethal due to severe vascular defects and delayed growth
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, induces the activation of the MEK/ERK pathway, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, involved in cellular stress response and JNK and p38 pathway activation, MLK1, 2 and 3 knockout mice show no obvious abnormalities, MLK 7 is activated in response to stressors like anisomycin and UV radiation and activates pro-apoptotic pathways through p38 and JNK
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates apoptosis in response to stress stimuli, knockout mice do not exhibit developmental defects, activates p38 and JNK pathways
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates p38,ERK1/2 and JNK, knockout embryos dying in utero due to abnormalities in vessel development and heart development, key regulator of cardiovascular and nervous system formation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulation of apoptosis, induction of the MEK/ERK pathway, promotes cell survival in the heart through modulation of MEKK5 activity, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, selctive for the activation of JNK and ERK5, knockout mutants are viable and fertile without apparent malformations, involved in T-cell receptor modulation and cytokine production in response to IgE
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + protein
ADP + phosphoprotein
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + c-Jun
ADP + phosphorylated c-Jun
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
MEK1 activates the ERK2 signaling pathway
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
-
activated MEK5 activates ERK5
-
-
?
ATP + MKK
ADP + phosphorylated MKK
-
induction of the JNK pathway activation
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + protein
ADP + phosphoprotein
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
BAD + ATP
BAD-phosphate + ADP
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
additional information
?
-
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
MKK4 activates the JNK signaling pathway
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21Waf1/Cip1-mediated growth arrest
-
-
?
additional information
?
-
-
MEKK2 and MEKK3 are involved in activation of signal transduction pathways via toll-like receptor TLR, mitogen-activated protein kinases MAPK, and NF-kappaB, overview
-
-
?
additional information
?
-
-
MEKK2 induces the JNK signaling pathway, overview
-
-
?
additional information
?
-
-
the enzyme is part of the MAPK signaling cascades, overview
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, overview, MEKK1 regulates calpain-dependent cell migration via regulation of th ERK2-dependent signaling pathway and binding to focal adhesions, actinin, and FAK, overview
-
-
?
additional information
?
-
-
endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress
-
-
?
additional information
?
-
-
induces activation of NF-kappaB reporter activity, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
involved in the activation of NF-kappaB, negatively regulates MEKK3-induced activation of NF-kappaB reporter activity, able to autophosphorylate at multiple sites when bound to TAB1, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK and JNK pathways in cells of the imune system in response to inflammatory mediators, knockout mice show normal development but defects in inflammatory response, involved in T-cell proliferation, probably involved in cardiac myocyte differentiation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK1/2 and possibly also ERK3, important function in vascular development, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK and p38MAP kinases in response to stress stimuli, knockout mice usually dying shortly after birth due to neural tube and skeletal malformations, functions in regulation of apoptosis and cell migration, possibly acts as central regulator of calcium-mediated signaling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK during neuronal migration in cerebal cortex development
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates the p38 pathway in response to stress and DNA damage
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, appears to transduce signals for JNK and ERK1/2 activation by pro-inflammatory stimuli and growth factors, key regulator of cell migration, deletion mutants are viable and fertile but display altered migration of epithelial cells resulting in defective eyelid closure, enzyme interacts directly with MEK1, MEK2 and c-Raf, involved in oxidative stress induced apoptosis in cardiac myocytes, enzyme deficiency individuals have diminished B-cell numbers, directly and indirectly involved in cell migration
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, important for the transduction of survival signals, involved in the regulation of apoptosis, important for TGFbeta signalling, deletion mutation in adult mice results in bone marrow and liver failure due to increased apoptosis of hematopoetic cells and hepatocytes, embryonic deletion is lethal due to severe vascular defects and delayed growth
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, induces the activation of the MEK/ERK pathway, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, involved in cellular stress response and JNK and p38 pathway activation, MLK1, 2 and 3 knockout mice show no obvious abnormalities, MLK 7 is activated in response to stressors like anisomycin and UV radiation and activates pro-apoptotic pathways through p38 and JNK
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates apoptosis in response to stress stimuli, knockout mice do not exhibit developmental defects, activates p38 and JNK pathways
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates p38,ERK1/2 and JNK, knockout embryos dying in utero due to abnormalities in vessel development and heart development, key regulator of cardiovascular and nervous system formation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulation of apoptosis, induction of the MEK/ERK pathway, promotes cell survival in the heart through modulation of MEKK5 activity, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, selctive for the activation of JNK and ERK5, knockout mutants are viable and fertile without apparent malformations, involved in T-cell receptor modulation and cytokine production in response to IgE
-
-
?
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C433A
-
completely abolishes its interaction with RhoA
C441A
-
site-directed mutagenesis, the mutant enzyme is not ubiquitinylated and thus shows a higher ERK activating activity
F571A
-
site-directed mutagenesis of MEKK2, inactive mutant
G452C/R454C/N455D
-
completely abolishes its interaction with RhoA
I1394/L1402A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
I1445A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
I1454A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
I573A
-
site-directed mutagenesis of MEKK2, inactive mutant
K1361R
-
shows remarkable increase in the number of neural tube defects
L1402A/F1443A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
L1458A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
L582A/P583A
-
site-directed mutagenesis of MEKK2, inactive mutant
P1452A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P1455A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P580A
-
site-directed mutagenesis of MEKK2, the mutant shows 82% of wild-type activity
P584A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
Q1405R/Q1406R
-
site-directed mutagenesis C-terminal to the subdomain VIII, creation of an optimal recognition site for protease furin, the mutant binds MKK4 more tightly than the wild-type enzyme, MKK4 binding protects the mutant enzyme from proteolytic cleavage
S1459A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
S519A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, inactive mutant
S526A
-
site-directed mutagenesis, MEKK3 phosphorylation site mutant, inactive mutant
S526A/K391M
-
critical phosphorylation site and catalytic site
T521A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
T523A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
T575A/Q576A/P577A
-
site-directed mutagenesis of MEKK2, inactive mutant
V586A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
F1443A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
F1443A
-
site-directed mutagenesis, subdomain X mutation, the mutant shows reduced activity compared to the wild-type enzyme
additional information
-
mutations in the MEKK subdomain X differentially affect MEKK2 and MEKK1 activity, overview
additional information
-
ASK1-/- cells, are resistant to TNF-induced apoptosis, produce low levels of TNF after LPS injection and are resistant to LPS-induced septic shock. In macrophages from TPL-2 deficient mice, activation of ERK is blocked following TLR4, TLR2 or TNFR1 stimulation, whereas activation of p38 and JNK via these receptors is unaffected, LPS upregulation of TNF is reduced, are resistant to endotoxin shock induced by LPS and D-galactosamine. TAK1-/- mice die early in uterus. Mlk3-/- mice are viable. In Mekk1-/- mice, normal or blocked JNK activation induced by TNF and IL-1, discrepancy in two different studies. MEKK3-deficient mice, embryonic lethal, activation of JNK and p38 is blocked, but not of ERK by IL-1 and TLR4
additional information
endogenous ASK2 constitutively degraded in ASK1-deficient cells, kinase-negative mutant of ASK1 effectively activates MAP2K and is more competent to respond to oxidative stress than ASK2 alone. Knockdown of ASK2 reveals that ASK2 is required for oxidative stress-induced JNK activation
additional information
-
Gckr-/- cells, have a significant defect in Wnt-mediated JNK activation and in induction of beta-catenin compared to wild-type
additional information
-
kinase inactive form of MEKK4, attenuates mesenchyme production
additional information
-
MEKK1-4 knockout mice, MEKK3 knockout is embryo-lethal, displaying inadequate fetal-maternal vascularization. MEKK4 knockout is largely perinatal lethal, and associated with defective neural tube closure, shows loss of JNK and p38 activation. MEKK1-2 knockouts are associated with impaired tissue remodeling associated with wound healing and homeostasis, expression of JunB and Fra-2 is markedly increased in MEKK1-deficient mouse fibroblasts. MLK3-deficient mice are viable and fertile with only a mild defect in the epidermal tissue of the dorsal midline. Mouse embryos deficient in either B-Raf or C-Raf die before day E12.5. A-Raf deficient mice die perinatally at 1-3 weeks of age. Tpl2-deficient mice are viable and appear indistinguishable from littermates, produce reduced levels of TNFalpha in response to LPS injection, are resistant to LPS/D-galactosamine-induced pathology. TAK1-deficient mouse embryo fibroblasts show decreased IL-1beta-induced IL-6 expression, TAK1-deficient keratinocytes develop a severe postnatal inflammation, loss of MEKK1 does not alter the course of tumorigenesis or inhibit primary tumor growth, intimal hyperplasia is significantly reduced
additional information
-
Mekk1deltaKD/deltaKD mice, MEKK1 ablation significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor 1, and restoration of cell-cell junctions of the wounded epidermis. Reconstituting MEKK1 expression with MEKK1 wild-type expression significantly accelerates wound closure
additional information
-
MEKK4-/- mice, protein is not essential for embryonic survival, but more than 80% of mice exhibit neural tube defects and die shortly after birth. Reduced level of IFN-gamma production in response to cytokine treatment. MEKK4-3R mutant, completely abolishes CIN85 interaction and is defective in activating the p38 pathway. Intermediate MKK6 causes reduction in p38 activation in response to both oxidative stress and epidermal growth factor stimulation, less prone to ubiquitination
additional information
generation of RhoA deletions in Map3k1 wild-type, heterozygous, and knockout genetic backgrounds
additional information
ZPK/DLK-deficient mice are derived from the gene-trap embryonic stem cell clone RRN366
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expressed as native and mutant FLAG-tag/HA-tag fusion protein in HEK293T cells, coexpression expreiments with TAK1
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expressed together with or without MEKK3 in HEK293T cells
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expression of a MEKK1 promoter-driven beta-Gal fusion protein in Mekk1deltaKD/deltaKD mice
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expression of GST-tagged full length MEKK2 and MEKK2 C-terminal and N-terminal fragments, i.e. of residues 1-619, 342-619, and 342-424, in COS-1 cells
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expression of HA-tagged active MEKK2 and inactive S519A MEKK2 mutant catalytic sites, expression of wild-type and mutant full length MEKK2s and of wild-type and mutant MEKK3s
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expression of His6-tagged MEKK1 subdomain VIII, comprising residues 1174-1493, His6-tagged wild-type, full-length enzyme, and His6-tagged mutant enzymes F1443A, I1394/L1402A, Q1405R/Q1406R, and L1402A/F1443A in HeLa and COS-1 cells
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full-length ASK2 cDNA inserted in pJG4-5, kinase-negative mutant of ASK1 inserted in pEG202. ASK1 and ASK2 constructs co-transformed along with the reporter plasmid pSH18-34 in EGY48 yeast strains, mutants transfected into HEK293 cells and MEF cells
HEK293 cells are transfected with pMap3k1-luc together with the expression vectors for active RhoA, dominant-negative RhoA, and ROCKII and treated with TGF-alpha, inhibition of histone deacetylase with sodium butyrate or trichostatin A increases luciferase expression in pMap3k1-luc transfected HEK293 cells. Molecular mechanism of Map3k1 promoter regulation, overview
into pBluescript, SF-9 insect cells infected with baculovirus expressing either MEKK4 or the kinase inactive form of MEKK4
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into PCR3.1 vector and expressed in HEK-293 cells
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MEKK1 fragments (1-132, 149-347, 149-636, 630-772, 766-1173, 766-1493, 1-719, and 565-1174) incorporated into pAS1CYH2 vector, expressed in Saccharomyces cerevisiae Y190 cells
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MEKK2, DNA and amino acid sequence determination, expression of wild-type and mutant MEKK2 by reticulocyte lysate TnT T7 mixture, expression of wild-type and mutant MEKK2 and MEKK1 in COS-1 cells and in HeLa cells, coexpression with ERK5 in COS-1 cells
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TAK1 expressed in HeLa cells
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TAK1 expression in HEK-293 cells, Ror2-Tak1 interaction analysis by expression in the yeast two-hybrid system
transient co-expression of MEKK1 and FAK in HEK293 cells
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wild-type and mutant enzyme
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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.
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7539-7548
1999
Mus musculus (P53349), Mus musculus
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Gerwins, P.; Blank, J.L.; Johnson, G.L.
Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway
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Mus musculus (O08648), Mus musculus
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Schweifer, N.; Valk, P.J.; Delwel, R.; Cox, R.; Francis, F.; Meier-Ewert, S.; Lehrach, H.; Barlow, D.P.
Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene
Genomics
43
285-297
1997
Mus musculus (O08648)
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Lange-Carter, C.A.; Pleiman, C.M.; Gardner, A.M.; Blumer, K.J.; Johnson, G.L.
A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf
Science
260
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1993
Mus musculus (P53349), Mus musculus
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Huang, J.; Tu, Z.; Lee, F.S.
Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity
Biochem. Biophys. Res. Commun.
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2003
Mus musculus
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Takeda, K.; Matsuzawa, A.; Nishitoh, H.; Ichijo, H.
Roles of MAPKKK ASK1 in stress-induced cell death
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23-29
2003
Caenorhabditis elegans, Homo sapiens, Mus musculus
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Cuevas, B.D.; Abell, A.N.; Witowsky, J.A.; Yujiri, T.; Johnson, N.L.; Kesavan, K.; Ware, M.; Jones, P.L.; Weed, S.A.; DeBiasi, R.L.; Oka, Y.; Tyler, K.L.; Johnson, G.L.
MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts
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22
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2003
Mus musculus
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Zhang, D.; Facchinetti, V.; Wang, X.; Huang, Q.; Qin, J.; Su, B.
Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways
EMBO J.
25
97-107
2006
Mus musculus
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Witowsky, J.A.; Johnson, G.L.
Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways
J. Biol. Chem.
278
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2003
Mus musculus
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Tu, Z.; Lee, F.S.
Subdomain VIII is a specificity-determining region in MEKK1
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278
48498-48505
2003
Mus musculus
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Cheng, J.; Yu, L.; Zhang, D.; Huang, Q.; Spencer, D.; Su, B.
Dimerization through the catalytic domain is essential for MEKK2 activation
J. Biol. Chem.
280
13477-13482
2005
Mus musculus
brenda
Fritz, A.; Brayer, K.J.; McCormick, N.; Adams, D.G.; Wadzinski, B.E.; Vaillancourt, R.R.
Phosphorylation of serine 526 is required for MEKK3 activity and association with 14-3-3 blocks dephosphorylation
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281
6236-6245
2006
Homo sapiens, Mus musculus, synthetic construct
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Du, J.; Cai, S.; Suzuki, H.; Akhand, A.A.; Ma, X.; Takagi, Y.; Miyata, T.; Nakashima, I.; Nagase, F.
Involvement of MEKK1/ERK/p21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal
J. Cell. Biochem.
88
1235-1246
2003
Homo sapiens, Mus musculus
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Stevens, M.V.; Parker, P.; Vaillancourt, R.R.; Camenisch, T.D.
MEKK4 regulates developmental EMT in the embryonic heart
Dev. Dyn.
235
2761-2770
2006
Mus musculus
brenda
Takeda, K.; Shimozono, R.; Noguchi, T.; Umeda, T.; Morimoto, Y.; Naguro, I.; Tobiume, K.; Saitoh, M.; Matsuzawa, A.; Ichijo, H.
Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1
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282
7522-7531
2007
Homo sapiens (O95382), Mus musculus (Q9WTR2)
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Bettinger, B.T.; Amberg, D.C.
The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems
J. Cell. Biochem.
101
34-43
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus
brenda
Chen, Z.; Cobb, M.H.
Activation of MEKK1 by Rho GTPases
Methods Enzymol.
406
468-478
2006
Homo sapiens, Mus musculus, synthetic construct
brenda
Deng, M.; Chen, W.L.; Takatori, A.; Peng, Z.; Zhang, L.; Mongan, M.; Parthasarathy, R.; Sartor, M.; Miller, M.; Yang, J.; Su, B.; Kao, W.W.; Xia, Y.
A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing
Mol. Biol. Cell
17
3446-3455
2006
Mus musculus
brenda
Shi, C.S.; Huang, N.N.; Harrison, K.; Han, S.B.; Kehrl, J.H.
The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes
Mol. Cell. Biol.
26
6511-6521
2006
Homo sapiens, Mus musculus, Mus musculus C57BL/6
brenda
Cuevas, B.D.; Abell, A.N.; Johnson, G.L.
Role of mitogen-activated protein kinase kinase kinases in signal integration
Oncogene
26
3159-3171
2007
Homo sapiens, Mus musculus, Rattus norvegicus, Xenopus sp.
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Symons, A.; Beinke, S.; Ley, S.C.
MAP kinase kinase kinases and innate immunity
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27
40-48
2006
Drosophila melanogaster, Homo sapiens, Mus musculus
brenda
Winkel, A.; Stricker, S.; Tylzanowski, P.; Seiffart, V.; Mundlos, S.; Gross, G.; Hoffmann, A.
Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling
Cell. Signal.
20
2134-2144
2008
Mus musculus (Q62073)
brenda
Di, Y.; Li, S.; Wang, L.; Zhang, Y.; Dorf, M.E.
Homeostatic interactions between MEKK3 and TAK1 involved in NF-kappaB signaling
Cell. Signal.
20
705-713
2008
Mus musculus
brenda
Craig, E.A.; Stevens, M.V.; Vaillancourt, R.R.; Camenisch, T.D.
MAP3Ks as central regulators of cell fate during development
Dev. Dyn.
237
3102-3114
2008
Mus musculus
brenda
Mongan, M.; Tan, Z.; Chen, L.; Peng, Z.; Dietsch, M.; Su, B.; Leikauf, G.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 protects against nickel-induced acute lung injury
Toxicol. Sci.
104
405-411
2008
Mus musculus
brenda
Itoh, A.; Horiuchi, M.; Wakayama, K.; Xu, J.; Bannerman, P.; Pleasure, D.; Itoh, T.
ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons
J. Neurosci.
31
7223-7228
2011
Mus musculus (Q60700)
brenda
Geh, E.; Meng, Q.; Mongan, M.; Wang, J.; Takatori, A.; Zheng, Y.; Puga, A.; Lang, R.A.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure
Proc. Natl. Acad. Sci. USA
108
17349-17354
2011
Mus musculus (P53349)
brenda