MAPK8
Description
The MAPK8 (mitogen-activated protein kinase 8) is a protein-coding gene located on chromosome 10.
Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
== Function == The protein encoded by this gene is a member of the MAP kinase and JNK 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 is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha-induced apoptosis. This kinase is also involved in UV radiation-induced apoptosis, which is thought to be related to the cytochrome c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternately spliced transcript variants encoding distinct isoforms have been reported. MAPK8 contains multiple amino acid sites that are phosphorylated and ubiquitinated.
== Interactions == MAPK8 has been shown to interact with:
== References ==
== Further reading ==
== External links == MAP Kinase Resource Archived 2021-04-15 at the Wayback Machine.
MAPK8, also known as JNK1, is a serine/threonine-protein kinase involved in a wide range of cellular processes, including cell proliferation, differentiation, migration, transformation, and programmed cell death. It plays a crucial role in the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway, which is triggered by extracellular stimuli like pro-inflammatory cytokines or physical stress. MAPK8 is activated by phosphorylation by the dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7, and it further phosphorylates various transcription factors, including components of the AP-1 complex like JUN, JDP2, and ATF2, thereby regulating AP-1 transcriptional activity. Additionally, MAPK8 phosphorylates the replication licensing factor CDT1, inhibiting its interaction with the histone H4 acetylase HBO1, which is essential for replication initiation. MAPK8 promotes stressed cell apoptosis by phosphorylating key regulatory factors such as p53/TP53 and YAP1. In T-cells, MAPK8 is required for the polarized differentiation of T-helper cells into Th1 cells. It also contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. MAPK8 mediates starvation-induced BCL2 phosphorylation, leading to BCL2 dissociation from BECN1 and the activation of autophagy. It also phosphorylates STMN2, regulating microtubule dynamics and controlling neurite elongation in cortical neurons. Furthermore, MAPK8 phosphorylates several other substrates including HSF4, SIRT1, ELK1, and ITCH, and it plays a role in the regulation of the circadian clock by phosphorylating the CLOCK-BMAL1 heterodimer. MAPK8 phosphorylates HSF1, suppressing HSF1-induced transcriptional activity, and it phosphorylates POU5F1, inhibiting its transcriptional activity and enhancing its proteasomal degradation. In neurons, MAPK8 phosphorylates SYT4, which captures neuronal dense core vesicles at synapses. MAPK8 phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly, and it phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity. Additionally, MAPK8 phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome, and it phosphorylates ALKBH5 in response to ROS, promoting its sumoylation and inactivation.
MAPK8 is also known as JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8, SAPK1, SAPK1c.
