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Information on EC 2.7.12.2 - mitogen-activated protein kinase kinase and Organism(s) Mus musculus and UniProt Accession Q61084
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2.7.12.2 mitogen-activated protein kinase kinaseIUBMB Comments
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues . 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
- 2.7.12.2
- mapks
- c-jun
- 3-kinase
- endothelial
- phosphatidylinositol
- mek1
- pkc
- necrosis
- agonist
- melanoma
- metastasis
- camp
- sirnas
- egf
- raf-1
- bcl-2
- cyclins
- c-fos
-
dominant-negative
- erk2
- rapamycin
-
stress-activated
-
phorbol
- wortmannin
- caspase-3
- nf-kappab
- phosphoinositide
- mtor
- trametinib
- creb
-
kinase-dependent
-
platelet-derived
- pertussis
-
mek-erk
-
brafv600e
-
ras-mediated
-
p21ras
- agriculture
- p38alpha
- elk-1
-
ras-induced
-
dual-specificity
-
extracellular-regulated
-
signal-related
-
p90rsk
-
ras-dependent
- drug development
- rsk
- medicine
- analysis
-
braf-mutant
-
egf-induced
- phospho-erk
-
erk-dependent
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
mek/erk, mitogen-activated protein kinase kinase, map kinase kinase, mapkk, mek-1, extracellular-signal-regulated kinase, mapk/erk kinase, map2k4, erk 1, mitogen-activated protein kinase kinase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dual specificity mitogen-activated protein kinase kinase 1
-
extracellular signal-regulated kinase
MEK
MEK1
MEK2
mitogen-activated protein kinase kinase 4
mitogen-activated protein kinase kinase/extracellular signalregulated kinase
-
-
MKK4
stress-activate protein kinase/extracellular signal-regulated protein kinase kinase-1
-
-
additional information
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKK-activated)
This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. 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
142805-58-1
-
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 + protein
ADP + phosphoprotein
MEKK 3 preferentially activates p42/44MAPK
-
-
?
ATP + c-Jun N-terminal kinase
ADP + phosphorylated c-Jun N-terminal kinase
JNK activation
-
-
?
ATP + Erk-1 gene product
ADP + phosphorylated Erk-1 gene product
phosphorylation primarily on a tyrosine residue and, to a lesser extent, on a threonine
-
?
ATP + JNK
ADP + phopsho-JNK
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + myelin basic protein kinase
ADP + phosphorylated myelin basic protein kinase
-
-
-
?
ATP + [ERK2 substrate peptide]
ADP + [ERK2 substrate peptide] phosphate
MEK1
-
-
?
ATP + [myelin basic protein substrate peptide]
ADP + [myelin basic protein substrate peptide] phosphate
-
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
phosphorylation by MEK activates ERK, which plays a role in pain induction modulating the A-type currents of potassium channels in neurons, ERK plays a central role in nocireceptive sensitization in the spinal cord
-
-
?
ATP + JNK
ADP + phospho-JNK
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + JNK
ADP + phospho-JNK
substrate of MKK4 and MKK7 in a synergistic manner
-
-
?
ATP + JNK
ADP + phosphorylated JNK
phosphorylation of JNK at the Thr residue located in the activation loop
-
-
?
ATP + JNK
ADP + phosphorylated JNK
phosphorylation of JNK at the Tyr residue located in the activation loop
-
-
?
ATP + p38
ADP + phospho-p38
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + protein
ADP + phosphoprotein
phosphorylates kinase-inactive Erk-1 protein primarily on a tyrosine residue and, to a lesser extent, on a threonine
-
-
?
ATP + protein
ADP + phosphoprotein
possible role for ASK1 in tissue development during embryogenesis as well as cytokine-induced apoptosis
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is the major activator for p38
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is involved on MAPK signal transduction pathway
-
-
?
ATP + protein
ADP + phosphoprotein
MEKK 2 preferentially activates JNK
-
-
?
additional information
?
-
-
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, which is involved in e.g. formalin-induced inflammatory pain and thermal hyperalgesia, overview
-
-
?
additional information
?
-
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
-
substrate binding via the D-domain of the MKK
-
-
?
additional information
?
-
substrate binding via the D-domain of the MKK
-
-
?
additional information
?
-
substrate binding via the D-domain of the MKK
-
-
?
additional information
?
-
MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation
-
-
?
additional information
?
-
MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation
-
-
?
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 + protein
ADP + phosphoprotein
MEKK 3 preferentially activates p42/44MAPK
-
-
?
ATP + c-Jun N-terminal kinase
ADP + phosphorylated c-Jun N-terminal kinase
JNK activation
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
phosphorylation by MEK activates ERK, which plays a role in pain induction modulating the A-type currents of potassium channels in neurons, ERK plays a central role in nocireceptive sensitization in the spinal cord
-
-
?
ATP + JNK
ADP + phopsho-JNK
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + JNK
ADP + phospho-JNK
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + p38
ADP + phospho-p38
the enzyme is involved in stress-activated MAP kinase pathways, tumorigenesis, and cancer acting as a metastasis suppressor, overview
-
-
?
ATP + JNK
ADP + phosphorylated JNK
phosphorylation of JNK at the Thr residue located in the activation loop
-
-
?
ATP + JNK
ADP + phosphorylated JNK
phosphorylation of JNK at the Tyr residue located in the activation loop
-
-
?
ATP + protein
ADP + phosphoprotein
possible role for ASK1 in tissue development during embryogenesis as well as cytokine-induced apoptosis
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is the major activator for p38
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is involved on MAPK signal transduction pathway
-
-
?
ATP + protein
ADP + phosphoprotein
MEKK 2 preferentially activates JNK
-
-
?
additional information
?
-
-
the enzyme is involved in the mitogen-activated protein kinase signaling pathway, which is involved in e.g. formalin-induced inflammatory pain and thermal hyperalgesia, overview
-
-
?
additional information
?
-
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
pro-oncogenic role of mitogen-activated protein kinase kinase 4 in cancer, overview. MKK4 is also involved in the immune system and development of B- and T-cells, as well as in cardiac hypertrophy, overview
-
-
?
additional information
?
-
MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation
-
-
?
additional information
?
-
MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(2,3-dihydroxypropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
1-(3-cyanopropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
1-ethyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
1-methyl-4-(2-naphthylamino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-1-(3-hydroxypropyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
-
4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-N,1-dimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-N,N,1-trimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-methylanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
-
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-amino-1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-2-hydroxybutan-1-one
-
4-[2-fluoro-4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)anilino]-1-methyl-6-oxo-1,6 -dihydro-3-pyridinecarboxamide
-
4-[2-fluoro-4-(3-hydroxypropyl)anilino]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
-
4-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-3-hydroxy-4-oxobutanamide
-
Cocoa procyanidin B2
procyanidin B2 suppresses TPA-induced phosphorylation of MEK, ERK, and p90RSK in JB6 P+ cells, suppresses JB6 P+ cell transformation by inhibiting mitogen-activated protein kinase kinase, molecular mechanism, overview
Cocoa procyanidins
suppresses JB6 P+ cell transformation by inhibiting mitogen-activated protein kinase kinase, molecular mechanisms of the chemopreventive potential of cocoa and its active ingredients, overview
-
ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
-
PD98059
-
inhibitor specific for MEK/ERK activation, granulocyte/macrophage colony number is decreased by ca. 60%
siRNA
-
knockdown of MEK, HSCs give rise to Mac-1+ myeloid cells less efficiently than control HSCs
-
tert-butyl [5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetate
-
[5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetic acid
-
U0126
-
inhibitor specific for MEK/ERK activation, granulocyte/macrophage colony number is decreased by ca. 60%
additional information
inactivated by the serine/threonine phosphatase 2A but not by the protein-tyrosine phosphatase 1B
-
additional information
inactivated by the serine/threonine phosphatase 2A but not by the protein-tyrosine phosphatase 1B
-
additional information
-
inactivated by the serine/threonine phosphatase 2A but not by the protein-tyrosine phosphatase 1B
-
additional information
-
treatment with LY294002, paclitaxel, or serum starvation does not induce apoptosis of wild-type MEF cells
-
additional information
-
design and synthesis of 4-anilino-5-carboxamido-2-pyridone MEK1 inhibitors using a combination of medicinal chemistry, computational chemistry, and structural elucidation, overview. Binding structure analysis, overview
-
additional information
design and synthesis of 4-anilino-5-carboxamido-2-pyridone MEK1 inhibitors using a combination of medicinal chemistry, computational chemistry, and structural elucidation, overview. Binding structure analysis, overview
-
additional information
design and synthesis of 4-anilino-5-carboxamido-2-pyridone MEK1 inhibitors using a combination of medicinal chemistry, computational chemistry, and structural elucidation, overview. Binding structure analysis, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
ERK and MEK are activated by phosphorylation, ERK is induced by formalin
-
additional information
-
MKKs are activated by phopshorylation through MKKKs, activation mechanism of MKK4 involving MEKK1, overview
-
additional information
MKKs are activated by phopshorylation through MKKKs, activation mechanism of MKK4 involving MEKK1, overview
-
additional information
MKKs are activated by phopshorylation through MKKKs, activation mechanism of MKK4 involving MEKK1, overview
-
additional information
-
MKKs are activated by phopshorylation through MKKKs, overview
-
additional information
MKKs are activated by phopshorylation through MKKKs, overview
-
additional information
MKKs are activated by phopshorylation through MKKKs, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
1-(2,3-dihydroxypropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
above, cascade IC50
0.00489 - 0.0049
1-(3-cyanopropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000091 - 0.01
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.0000174
3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
Mus musculus
cascade IC50
0.00254 - 0.005
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.003
4-(2-fluoro-4-iodoanilino)-1-(3-hydroxypropyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000004 - 0.000023
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000425 - 0.005
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
0.00113
4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.00043 - 0.00254
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
0.000627 - 1.2
4-(2-fluoro-4-iodoanilino)-N,N,1-trimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000005 - 0.000018
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.00018 - 0.00021
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000061 - 0.000095
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.00015 - 0.00036
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
0.0039 - 0.00572
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000093 - 0.00191
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.00012 - 0.00363
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.00011 - 0.00262
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.000021 - 0.0001
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.0000842
4-amino-1-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-2-hydroxybutan-1-one
Mus musculus
cascade IC50
0.01
4-[2-fluoro-4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)anilino]-1-methyl-6-oxo-1,6 -dihydro-3-pyridinecarboxamide
0.01
4-[2-fluoro-4-(3-hydroxypropyl)anilino]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
0.0000012
4-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl]-3-hydroxy-4-oxobutanamide
Mus musculus
cascade IC50
0.000063 - 0.00067
ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
0.01
tert-butyl [5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetate
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.01
[5-(aminocarbonyl)-4-(2-fluoro-4-iodoanilino)-2-oxo-1(2H)-pyridinyl]acetic acid
Mus musculus
above, cascade IC50
0.00489
1-(3-cyanopropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.0049
1-(3-cyanopropyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000091
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00601
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.01
1-allyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.001
1-ethyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.001
1-ethyl-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.003
1-methyl-4-(2-naphthylamino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.003
1-methyl-4-(2-naphthylamino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00254
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.005
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.005
4-(2-fluoro-4-iodoanilino)-1-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
above cascade IC50
0.003
4-(2-fluoro-4-iodoanilino)-1-(3-hydroxypropyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.003
4-(2-fluoro-4-iodoanilino)-1-(3-hydroxypropyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
above, cascade IC50
0.000004
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.000023
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000023
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000425
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000425
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
Mus musculus
cascade IC50
0.005
4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
Mus musculus
colon26 cellular assay
0.00113
4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00113
4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.0001
4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.0001
4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00063
4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.00043
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.00254
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00254
4-(2-fluoro-4-iodoanilino)-6-oxo-1-propyl-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000195
4-(2-fluoro-4-iodoanilino)-N,1-dimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000195
4-(2-fluoro-4-iodoanilino)-N,1-dimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000627
4-(2-fluoro-4-iodoanilino)-N,N,1-trimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
1.2
4-(2-fluoro-4-iodoanilino)-N,N,1-trimethyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000005
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.000018
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000018
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00018
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.000206
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00021
4-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000061
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000061
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000095
4-(2-fluoro-4-iodoanilino)-N-(3-hydroxypropyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assayy
0.00297
4-(2-fluoro-4-methylanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00297
4-(2-fluoro-4-methylanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00015
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.000356
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00036
4-(2-fluoro-4-methylsulfanylphenylamino)-1-methyl-6-oxo-1,6-dihydro-3 -pyridinecarboxamide
Mus musculus
cascade IC50
0.0039
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.0057
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00572
4-(3,4-dichlorophenylamino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000093
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.0019
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.00191
4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00012
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.00363
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00363
4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.01
4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.01
4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
above, cascade IC50
0.00011
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.00262
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.00262
4-(4-ethyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.000021
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
colon26 cellular assay
0.0001
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.0001
4-(4-ethynyl-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
cascade IC50
0.01
4-[2-fluoro-4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)anilino]-1-methyl-6-oxo-1,6 -dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.01
4-[2-fluoro-4-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)anilino]-1-methyl-6-oxo-1,6 -dihydro-3-pyridinecarboxamide
Mus musculus
above, cascade IC50
0.01
4-[2-fluoro-4-(3-hydroxypropyl)anilino]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.01
4-[2-fluoro-4-(3-hydroxypropyl)anilino]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
Mus musculus
above, cascade IC50
0.000016
CI-1040
Mus musculus
clinical candidate, inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
0.000063
ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
Mus musculus
colon26 cellular assay
0.000669
ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
Mus musculus
inhibition of the Raf-MEK-ERK cascade in an isolated enzyme assay
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Mkk4 transcripts confined to the central nervous system in early embryogenesis, up to embryonic day 10
17 days post coitum, expression of ASK1 in developing skin, cartilage and bone
high expression of MKK4 in the epithelium but not in the stromal compartment
-
epididymal spermatozoa, 60000 Da variant of MAP3K11, may be a result of proteolytic cleavage of the longer form
-
93000, 70000, 40000, 23000 Da forms, first MAP3K11 expression detectable at day-14, higher levels of expression at day-30 and day-36
additional information
high expression level of MKK4, expression in adult and fetal brain
expression at low levels in adult brain, expression at high levels in neonatal brain
in later embryogenesis, starting at day 12, Mkk4 becomes highly expressed in the developing liver coincident with a period of active differentiation and an increase in liver size
high expression level of MKK4, expression in adult and fetal liver
additional information
-
not in spermatogonia, early primary spermatocytes, Sertoli cells, or peritubular myoid cells
additional information
-
NSCLC cell lines H1299, H226B, H226Br, H332, H358, H460, A549, H596, and Calu-6
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
developing spermatids and epididymal spermatozoa, colocalization of MAP3K11 and CRISP2
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
signal transduction pathways are integral components of the developmental regulatory network that guides progressive cell fate determination. Essential enzymes MKK4 and MKK7 are upstream kinases of the mitogen-activated protein kinases (MAPKs), responsible for channeling physiological and environmental signals to their cellular responses. In vitro, MKK4 and MKK7 are dispensable for in embryonic stem cell self-renewal and pluripotency maintenance, but they exhibit unique signaling and functional properties in differentiation. MKK4 and MKK7 complemented each other in activation of the JNK-c-Jun cascades and loss of both leads to senescence upon cell differentiation.On the other hand, MKK4 and MKK7 have opposite effects on activation of the p38 cascades during differentiation, MKK4 is required for cardiomyocyte differentiation, while MKK7 represses it
physiological function
malfunction
enzyme mutants show embryonic lethality. Mkk4 knockout embryonic stem cells exhibit diminished p-ATF2 and MEF2C expression, resulting in impaired MHC induction and defective cardiomyocyte differdifferentiation. Loss of MKK4 significantly blocks the induction of Mhca and Mhcb, but had no effect on expression of Mlc. Exogenous MKK4 expression partially restores the ability of Mkk4-/- embryonic stem cells to differentiate into cardiomyocytes. Mice lacking either MKK4 or MKK7 display an analogous embryonic lethal phenotype that may be attributed, at least in part, to insufficient JNK activation
malfunction
enzyme mutants show embryonic lethality. Mkk7 knockout embryonic stem cells show elevated phosphorylation of MKK4, p38, and ATF2, and increased MEF2C expression. The mutant cells show higher expression of MHC and MLC and enhanced formation of contractile cardiomyocytes. Mice lacking either MKK4 or MKK7 display an analogous embryonic lethal phenotype that may be attributed, at least in part, to insufficient JNK activation
malfunction
genetic inactivation of MKK7 results in an extended period of oscillation in circadian gene expression in mouse embryonic fibroblasts, genetic inactivation of the Mkk7 gene alters circadian gene expression
physiological function
MKK4 regulates Jun N-terminal kinase (JNK) and differentiating cell survival. And MKK4 is required for p38 activation and cardiomyocyte differentiation. Enzymes MKK4 and MKK7 have complementary and distinct roles in embryonic stem cell differentiation
physiological function
MKK7 regulates Jun N-terminal kinase (JNK) and differentiating cell survival. Enzymes MKK4 and MKK7 have complementary and distinct roles in embryonic stem cell differentiation. MKK7 reduces p38 activation
physiological function
the stress kinase mitogen-activated protein kinase kinase 7 (MKK7) is a specific activator of c-Jun N-terminal kinase (JNK), which controls various physiological processes, such as cell proliferation, apoptosis, differentiation, and migration. Involvement of stress kinase mitogen-activated protein kinase kinase 7 in regulation of mammalian circadian clock, overview. JNK interacts with PER2 at both the exogenous and endogenous levels, and MKK7-mediated JNK activation increases the half-life of PER2 protein by inhibiting its ubiquitination. The PER2 protein stabilization induced by MKK7-JNK fusion protein reduces the degradation of PER2 induced by casein kinase 1epsilon. MKK7 controls circadian gene expression in cultured cells
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
MKKs are activated by phopshorylation through MKKKs, e.g. MEKK, MLK, TAK1, Ask1, or TPL2
phosphoprotein
MKKs are activated by phopshorylation through MKKKs, e.g. MEKK, MLK, TAK1, Ask1, or TPL2, MKK4 is phopshorylated at serine and threonine residues in the SIAKT motif
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
expression of the neuron-specific dominant negative mitogen activated protein kinase kinase in mutant mice leads to impaired inflammatory pain and thermal hyperalgesia
additional information
-
MKK4-null MEF cells, are highly susceptible to apoptosis by LY294002, paclitaxel, or serum starvation. MKK4 loss increases PTEN expression and inhibits PI3K-dependent signaling but reveals persistent AKT phosphorylation in serum-starved MKK4-null cells
additional information
-
targeted deletion of the Mkk4 gene, results in early embryonic lethality, anemia, severe hemorrhaging in the liver, impaired liver formation and abnormal hepatogenesis, which correlates with significant apoptosis of liver cells, and greatly reduced thymus size. In Mkk4-/- embryonic stem cells there is no defect in p38 activation in response to a number of stresses
additional information
targeted deletion of the Mkk4 gene, results in early embryonic lethality, anemia, severe hemorrhaging in the liver, impaired liver formation and abnormal hepatogenesis, which correlates with significant apoptosis of liver cells, and greatly reduced thymus size. In Mkk4-/- embryonic stem cells there is no defect in p38 activation in response to a number of stresses
additional information
targeted deletion of the Mkk4 gene, results in early embryonic lethality, anemia, severe hemorrhaging in the liver, impaired liver formation and abnormal hepatogenesis, which correlates with significant apoptosis of liver cells, and greatly reduced thymus size. In Mkk4-/- embryonic stem cells there is no defect in p38 activation in response to a number of stresses
additional information
-
construction of MKK4-deficient mutant mice, phenotype, overview
additional information
construction of MKK4-deficient mutant mice, phenotype, overview
additional information
construction of MKK4-deficient mutant mice, phenotype, overview
additional information
construction of MKK4 gene knockout mice, that show embryonic lethality
additional information
construction of MKK4 gene knockout mice, that show embryonic lethality
additional information
construction of MKK7 gene knockout mice, that show embryonic lethality
additional information
construction of MKK7 gene knockout mice, that show embryonic lethality
additional information
exogenous expression in cultured mammalian cells of an MKK7-JNK fusion protein, that functions as a constitutively active form of JNK, induces phosphorylation of PER2, an essential circadian component
additional information
-
exogenous expression in cultured mammalian cells of an MKK7-JNK fusion protein, that functions as a constitutively active form of JNK, induces phosphorylation of PER2, an essential circadian component
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
constitutive active form of MEK1 and siRNA-targeting MEK1 cloned into MSCV-IRES-GFP vector, retrovirally transduced to HSCs and injected into sublethally irradiated RAG2-/- (CD42.2) mice
-
gene Mkk4, expression in ovarian cancer cell line SKOV3ip.1, that lacks endogenous MKK4, leading to a decrease in overt metastatic implants on several tissues and organs
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
design and synthesis of a new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones
medicine
acts as tumor suppressor, but can also promote tumor growth, plays a role in liver formation, the immune system and cardiac hypertrophy, contributes to optimal c-Jun N-terminal kinase activation
additional information
additional information
-
MEK/ERK pathway plays an important role in myeloid differentiation, especially granulocyte/macrophage lineage commitment, not only in ectopic interleukin-2 driven lineage conversion in common lymphoid progenitors but also in physiologic hematopoiesis
additional information
-
MKK4 promotes the survival of MEF cells by decreasing the expression of phosphatase and tensin homologue deleted from chromosome 10 PTEN. MKK4 inhibits PTEN transcription by activating NFkappaB, a transcriptional suppressor of PTEN. MKK4 is required for nuclear translocation of RelA/p65 and processing of the NFkappaB2 precursor p100 into the mature form p52. MKK4 promotes cell survival by activating phosphatidylinositol 3-kinase through an NFkappaB/PTEN-dependent pathway
additional information
-
the carboxyl-most 20 amino acids of MAP3K11 interact with the CRISP domain of CRISP2. CRISP2 may be a MAP3K11-modifying protein or, alternatively, MAP3K11 acts to phosphorylate CRISP2 during acrosome development
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kawai, J.; Shinagawa, A.; Shibata, K.; Yoshino, M.; Itoh, M.; et al.
Functional annotation of a full-length mouse cDNA collection
Nature
409
685-690
2001
Mus musculus (O09110)
Moriguchi, T.; Toyoshima, F.; Gotoh, Y.; Iwamatsu, A.; et al.
Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2
J. Biol. Chem.
271
26981-26988
1996
Mus musculus (O09110), Mus musculus, Homo sapiens (P46734)
Tobiume, K.; Inage, T.; Takeda, K.; Enomoto, S.; Miyazono, K.; Ichijo, H.
Molecular cloning and characterization of the mouse apoptosis signal-regulating kinase 1
Biochem. Biophys. Res. Commun.
239
905-910
1997
Mus musculus (O35099)
Crews, C.M.; Alessandrini, A.; Erikson, R.L.
The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product
Science
258
478-480
1992
Mus musculus (P31938)
Crews, C.M.; Erikson, R.L.
Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product
Proc. Natl. Acad. Sci. USA
89
8205-8209
1992
Mus musculus (P31938), Mus musculus (Q63932), Mus musculus
Duesbery, N.S.; Webb, C.P.; Leppla, S.H.; Gordon, V.M.; Klimpel, K.R.; Copeland, T.D.; Ahn, N.G.; Oskarsson, M.K.; Fukasawa, K.; Paull, K.D.; Vande Woude, G.F.
Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor
Science
280
734-737
1998
Mus musculus (P31938), Homo sapiens (P36507), Homo sapiens (Q02750)
Sanchez, I.; Hughes, R.T.; Mayer, B.J.; Yee, K.; Woodgett, J.R.; Avruch, J.; Kyriakis, J.M.; Zon, L.I.
Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun
Nature
372
794-798
1994
Mus musculus (P47809)
Cuenda, A.; Alonso, G.; Morrice, N.; Jones, M.; Meier, R.; Cohen, P.; Nebreda, A.R.
Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells
EMBO J.
15
4156-4164
1996
Homo sapiens (P52564), Homo sapiens, Mus musculus (P70236), Mus musculus
Blank, J.L.; Gerwins, P.; Elliott, E.M.; Sather, S.; Johnson, G.L.
Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase
J. Biol. Chem.
271
5361-5368
1996
Mus musculus (Q61083), Mus musculus (Q61084)
Brott, B.K.; Alessandrini, A.; Largaespada, D.A.; Copeland, N.G.; Jenkins, N.A.; Crews, C.M.; Erikson, R.L.
MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues
Cell Growth Differ.
4
921-929
1993
Mus musculus (Q63932)
Karim, F.; Hu, H.J.; Adwanikar, H.; Kaplan, D.R.; Gereau, R.W.T.
Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK)
Mol. Pain
2
2
2006
Mus musculus
Gibbs, G.M.; Bianco, D.M.; Jamsai, D.; Herlihy, A.; Ristevski, S.; Aitken, R.J.; Kretser, D.M.; OBryan, M.K.
Cysteine-rich secretory protein 2 binds to mitogen-activated protein kinase kinase kinase 11 in mouse sperm
Biol. Reprod.
77
108-114
2007
Mus musculus
Hsu, C.L.; Kikuchi, K.; Kondo, M.
Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment
Blood
110
1420-1428
2007
Mus musculus
Xia, D.; Srinivas, H.; Ahn, Y.H.; Sethi, G.; Sheng, X.; Yung, W.K.; Xia, Q.; Chiao, P.J.; Kim, H.; Brown, P.H.; Wistuba, I.I.; Aggarwal, B.B.; Kurie, J.M.
Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expression through an NF kappa B-dependent pathway
J. Biol. Chem.
282
3507-3519
2007
Mus musculus
Spicer, J.A.; Rewcastle, G.W.; Kaufman, M.D.; Black, S.L.; Plummer, M.S.; Denny, W.A.; Quin, J.; Shahripour, A.B.; Barrett, S.D.; Whitehead, C.E.; Milbank, J.B.; Ohren, J.F.; Gowan, R.C.; Omer, C.; Camp, H.S.; Esmaeil, N.; Moore, K.; Sebolt-Leopold, J.S.; Pryzbranowski, S.; Merriman, R.L.; Ortwine, D.F.; Warmus,
4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase
J. Med. Chem.
50
5090-5102
2007
Mus musculus, Mus musculus (P31938), Mus musculus (Q63932)
Whitmarsh, A.J.; Davis, R.J.
Role of mitogen-activated protein kinase kinase 4 in cancer
Oncogene
26
3172-3184
2007
Drosophila melanogaster, Homo sapiens, Homo sapiens (O14733), Homo sapiens (P45985), Mus musculus, Mus musculus (P47809), Mus musculus (Q8CE90), Rattus norvegicus, Xenopus laevis
Kang, N.J.; Lee, K.W.; Lee, D.E.; Rogozin, E.A.; Bode, A.M.; Lee, H.J.; Dong, Z.
Cocoa procyanidins suppress transformation by inhibiting mitogen-activated protein kinase kinase
J. Biol. Chem.
283
20664-20673
2008
Mus musculus (P31938), Mus musculus
Wang, J.; Chen, L.; Ko, C.I.; Zhang, L.; Puga, A.; Xia, Y.
Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation
J. Biol. Chem.
287
2787-2797
2012
Mus musculus (P47809), Mus musculus (Q8CE90)
Uchida, Y.; Osaki, T.; Yamasaki, T.; Shimomura, T.; Hata, S.; Horikawa, K.; Shibata, S.; Todo, T.; Hirayama, J.; Nishina, H.
Involvement of stress kinase mitogen-activated protein kinase kinase 7 in regulation of mammalian circadian clock
J. Biol. Chem.
287
8318-8326
2012
Homo sapiens (O14733), Mus musculus (Q8CE90), Mus musculus
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Release 2023.1 (January 2023)
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