MAP2K4
Entrez ID: 6416
Full name: mitogen-activated protein kinase kinase 4
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: STE: STE7: MEK4
Chromosomal location: 17p12
Substructure location: Gatekeeper: 178 A-loop: 246...268 G-loop: 108...114 αC-helix: 139...153
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MAP2K4
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activa...
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
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GO - Biological processes (BP):
activation of JUN kinase activity, activation of MAPK activity, activation of protein kinase activity, apoptotic process, cell growth involved in cardiac muscle cell development, cellular response to mechanical stimulus, cellular response to sorbitol, Fc-epsilon receptor signaling pathway, JNK casca...
activation of JUN kinase activity, activation of MAPK activity, activation of protein kinase activity, apoptotic process, cell growth involved in cardiac muscle cell development, cellular response to mechanical stimulus, cellular response to sorbitol, Fc-epsilon receptor signaling pathway, JNK cascade, negative regulation of motor neuron apoptotic process, positive regulation of DNA replication, positive regulation of neuron apoptotic process, positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of smooth muscle cell apoptotic process, regulation of mitotic cell cycle, response to wounding, signal transduction, signal transduction by protein phosphorylation, stress-activated protein kinase signaling cascade
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GO - Molecular function (MF):
ATP binding, JUN kinase kinase activity, MAP kinase kinase activity, mitogen-activated protein kinase kinase kinase binding, protein kinase activity, protein serine/threonine kinase activity, protein tyrosine kinase activity...
ATP binding, JUN kinase kinase activity, MAP kinase kinase activity, mitogen-activated protein kinase kinase kinase binding, protein kinase activity, protein serine/threonine kinase activity, protein tyrosine kinase activity
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GO - Cellular component (CC):
cytosol, nucleus, axon, cytoplasm, dendrite cytoplasm, perikaryon...
cytosol, nucleus, axon, cytoplasm, dendrite cytoplasm, perikaryon
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mitogen-activated protein kinase kinase 4
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*NOTE: the Kaplan plots were collected from OncoLnc