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Mitogen-activated protein kinase 9

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death^{1,2,3,4,5,6,7}. 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^{8,9,10,11,12,13,14}. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 (By similarity). 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 (By similarity). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (By similarity). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (By similarity). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells¹⁵. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels¹⁶. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (By similarity). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (By similarity). Also participates in neurite growth in spiral ganglion neurons¹⁷. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock¹⁸. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation¹⁹. Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (By similarity).

AlphaFold DB , UniProt , Accession Q9WTU6, Species MOUSE (Mus musculus, Mouse), Gene Mapk9, Length 423 aa.