Mitogen-activated protein kinase 9

Mitogen-activated protein kinase 9

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death10376527,15805466,17525747,19675674,20595622,21364637,22441692,34048572. 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/JNK210376527,15805466,17525747,19675674,20595622,21364637,22441692,34048572. 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 activity10376527. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN315805466. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP117525747,21364637. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells19290929. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels19290929. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption20595622. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway19675674. Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock22441692. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation34048572

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

Quoted from UniProt’s FUNCTION annotation for P45984 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Plasma membrane
• Cytosol
• Nuclear specklesadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm · Nucleus