MAPK9

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]

Mitogen-Activated Protein Kinase 9

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory 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).
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity).
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.

Cellular response to cadmium ionManual Assertion Based On ExperimentIMP:CAFA
Cellular response to reactive oxygen speciesManual Assertion Based On ExperimentIMP:CAFA
Cellular senescenceTAS:Reactome
Fc-epsilon receptor signaling pathwayTAS:Reactome
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
JNK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:CAFA
Positive regulation of apoptotic signaling pathwayIEA:Ensembl
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of macrophage derived foam cell differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of podosome assemblyIEA:Ensembl
Positive regulation of protein ubiquitinationIEA:Ensembl
Positive regulation of transcription factor catabolic processIEA:Ensembl
Protein localization to tricellular tight junctionIEA:Ensembl
Protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of circadian rhythmISS:UniProtKB
Regulation of DNA-binding transcription factor activityTAS:Reactome
Rhythmic processIEA:UniProtKB-KW

Cytoplasm
Nucleus
Colocalizes with POU5F1 in the nucleus.

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro.