Aliases for MAPK9 Gene
External Ids for MAPK9 Gene
Previous HGNC Symbols for MAPK9 Gene
Previous GeneCards Identifiers for MAPK9 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 targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Sep 2008]
GeneCards Summary for MAPK9 Gene
MAPK9 (Mitogen-Activated Protein Kinase 9) is a Protein Coding gene. Among its related pathways are PI-3K cascade and MAPK signaling pathway. GO annotations related to this gene include transcription factor binding and mitogen-activated protein kinase kinase kinase binding. An important paralog of this gene is MAPK11.
UniProtKB/Swiss-Prot for MAPK9 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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it
JNKs (c-Jun N-terminal kinases) are a group of mitogen-activated protein kinases (MAPKs), originally called stress activated protein kinases (SAPKs), because they are activated by a variety of environmental stresses. They are also activated in response to cytokines such as TNF-alpha and IL-1, and growth factors. There are three isoforms of JNK; JNK1, JNK2 and JNK3. JNK1 and JNK2 are ubiquitously expressed, whilst JNK3 expression is limited to the brain, heart and testis. JNK phosphorylates a wide variety of substrates including c-Jun. c-Jun is a component of the AP-1 transcription factor complex and is involved in the control cell proliferation, transformation, survival and death. JNK also phosphorylates p53 and some non-nuclear proteins. JNK-mediated phosphorylation of target proteins is essential for the induction of gene expression of interleukins, VEGF, COX-2, MMP-9, heme oxygenase-1, ICAM-1, NCX1, GnRHR and others. JNK is critical in processes as divergent as apoptosis, cell survival, proliferation and differentiation. The JNK pathway appears to be involved in inflammatory and autoimmune disorders including rheumatoid arthritis, irritable bowel disease, and atherosclerosis.