Human Mitogen Activated Protein Kinase 9, MAPK9 ELI

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).

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.