MAPK9

Description

The MAPK9 (mitogen-activated protein kinase 9) is a protein-coding gene located on chromosome 5.

Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene.

== Function == 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. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

== Interactions == Mitogen-activated protein kinase 9 has been shown to interact with:

Grb2, MAPK8IP1, MAPK8IP2, MAPK8IP3 P53, and TOB1.

MAPK9, also known as JNK2, is a serine/threonine-protein kinase that plays a crucial role in various cellular processes, including proliferation, differentiation, migration, transformation, and programmed cell death. It is activated by extracellular stimuli such as pro-inflammatory cytokines or physical stress, triggering the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this pathway, MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. MAPK9/JNK2 subsequently phosphorylates transcription factors, primarily components of AP-1 like JUN and ATF2, thus regulating AP-1 transcriptional activity. It also inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 in response to oxidative or ribotoxic stresses. Furthermore, MAPK9 promotes stressed cell apoptosis by phosphorylating key regulatory factors such as TP53 and YAP1. In T-cells, MAPK9, along with MAPK8, is essential for the polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, MAPK9 is activated by CARMA1, BCL10, MAP2K7, and MAP3K7/TAK1, regulating JUN protein levels. MAPK9 also plays a vital role in the disruption of epithelial tight-junctions induced by osmotic stress. When activated, it promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Additionally, MAPK9 is involved in neurite growth in spiral ganglion neurons and regulates the circadian clock by phosphorylating the CLOCK-BMAL1 heterodimer. MAPK9 phosphorylates POU5F1, inhibiting its transcriptional activity and enhancing its proteasomal degradation. It is found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1, and MAPK8/JNK1.

MAPK9 is also known as JNK-55, JNK2, JNK2A, JNK2ALPHA, JNK2B, JNK2BETA, PRKM9, SAPK, SAPK1a, p54a, p54aSAPK.

Associated Diseases

WES Whole Exome Sequencing