Aliases for MAPK8 Gene
External Ids for MAPK8 Gene
Previous Symbols for MAPK8 Gene
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jun 2013]
GeneCards Summary for MAPK8 Gene
MAPK8 (Mitogen-Activated Protein Kinase 8) is a Protein Coding gene. Diseases associated with MAPK8 include frozen shoulder and cisplatin toxicity. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include protein serine/threonine kinase activity and JUN kinase activity. An important paralog of this gene is MAPK11.
UniProtKB/Swiss-Prot for MAPK8 Gene
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).
JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms
MAPKs (mitogen-activated protein kinases) are serine-threonine kinases that regulate a wide variety of cellular functions. Six groups of MAPK have so far been identified: Extracellular signal-regulated kinases (ERK1, ERK2), c-Jun N-terminal kinases (JNKs), p38 isoforms (MAPK11, MAPK12, MAPK13, MAPK14), ERK5 (MAPK7), ERK3 (MAPK6) and ERK4 (MAPK4) and ERK7/8 (MAPK15). ERK 1 and ERK 2 transduce signals from growth factors and are key in regulating differentiation and proliferation in many cell types. Upon activation by MEK, ERK1 and 2 translocate to the nucleus where they phosphorylate transcription factors such as Elk1 and downstream kinases such as p90 RSK. JNK 1,2 and 3 (sometimes known as SAPKs or stress-activated kinases) and the p38 MAPKs (alpha-, beta-, delta and gamma- isoforms) are activated by UV irradiation, inflammatory cytokines and hyperosmolarity. The p38 MAPKs are also activated by lipopolysaccharide. Dysregulation of MAPK kinase pathways has been associated with various diseases including cancer (ERK), neurodegeneration (JNK) and inflammation (p38).