MAPK8
Entrez ID: 5599
Full name: mitogen-activated protein kinase 8
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: CMGC: MAPK: JNK
Chromosomal location: 10q11.22
Substructure location: Gatekeeper: 108 A-loop: 168...178, 182...190 G-loop: 32...38 αC-helix: 60...62
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MAPK8
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal ki...
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity).
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GO - Biological processes (BP):
cellular response to amino acid starvation, cellular response to cadmium ion, cellular response to cytokine stimulus, cellular response to lipopolysaccharide, cellular response to mechanical stimulus, cellular response to reactive oxygen species, Fc-epsilon receptor signaling pathway, intracellular ...
cellular response to amino acid starvation, cellular response to cadmium ion, cellular response to cytokine stimulus, cellular response to lipopolysaccharide, cellular response to mechanical stimulus, cellular response to reactive oxygen species, Fc-epsilon receptor signaling pathway, intracellular signal transduction, JNK cascade, JUN phosphorylation, negative regulation of apoptotic process, negative regulation of protein binding, peptidyl-serine phosphorylation, peptidyl-threonine phosphorylation, positive regulation of apoptotic process, positive regulation of cyclase activity, positive regulation of deacetylase activity, positive regulation of gene expression, positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway, positive regulation of protein metabolic process, protein phosphorylation, regulation of circadian rhythm, regulation of DNA-binding transcription factor activity, regulation of DNA replication origin binding, regulation of gene expression, regulation of macroautophagy, regulation of protein localization, response to mechanical stimulus, response to UV, rhythmic process, stress-activated MAPK cascade
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GO - Molecular function (MF):
ATP binding, enzyme binding, histone deacetylase binding, histone deacetylase regulator activity, JUN kinase activity, kinase activity, MAP kinase activity, protein serine/threonine kinase activity...
ATP binding, enzyme binding, histone deacetylase binding, histone deacetylase regulator activity, JUN kinase activity, kinase activity, MAP kinase activity, protein serine/threonine kinase activity
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GO - Cellular component (CC):
cytosol, mitochondrion, nucleoplasm, nucleus, axon, basal dendrite, cell junction, cytoplasm, synapse...
cytosol, mitochondrion, nucleoplasm, nucleus, axon, basal dendrite, cell junction, cytoplasm, synapse
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mitogen-activated protein kinase 8
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*NOTE: the Kaplan plots were collected from OncoLnc