MAPK15

Description

The MAPK15 (mitogen-activated protein kinase 15) is a protein-coding gene located on chromosome 8.

Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 gene. Evolutionarily, MAPK15 is conserved in a number of species, including P. troglodytes, B. taurus, M. musculus, R. norvegicus, D. rerio, D. melanogaster, C. elegans, and X. laevis.

== Function == The protein encoded by this gene is a member of the MAP (mitogen-activated protein) kinase family. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling cascades that regulate a number of cellular processes, including proliferation, differentiation, and transcriptional regulation. MAPK15 is often referred to as ERK7 or ERK8, and the latter two share 69% amino acid sequence similarity; at least one study has suggested that the two are, in fact, distinct proteins. In vertebrate models, ERK8 is not constitutively active, and exhibits relatively low basal kinase activity. It contains two SH3 (SRC homology 3) binding motifs in its C-terminal region, and is likely activated by an SRC-dependent signaling pathway. SRC is a non-receptor tyrosine kinase (and proto-oncogene) that has been implicated in cancer growth and progression in humans when it is overexpressed. The exact function of MAPK15 is unknown, though a number of studies have implicated the enzyme in various cellular pathways. Specifically, MAPK15 expression is significantly reduced in human lung and breast carcinomas, and MAPK15 down-regulation is correlated with increased cell motility.

MAPK15, an atypical MAPK protein, plays a critical role in regulating a variety of cellular processes, including autophagy, ciliogenesis, protein trafficking and secretion, and genome integrity. This regulation is largely dependent on its kinase activity. MAPK15 controls both basal and starvation-induced autophagy through its interactions with GABARAP, MAP1LC3B, and GABARAPL1, leading to the formation of autophagosomes, the degradation of SQSTM1, and the reduction of inhibitory phosphorylation of MAP1LC3B. It regulates the formation of primary cilia and the localization of ciliary proteins involved in cilium structure, transport, and signaling. MAPK15 also prevents the relocation of sugar-adding enzymes from the Golgi apparatus to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins. Additionally, under conditions of amino acid starvation, it mediates the disassembly of the transitional endoplasmic reticulum site and inhibits secretion. MAPK15 binds to chromatin, which leads to its activation and interaction with PCNA. This interaction helps protect genomic integrity by inhibiting the MDM2-mediated degradation of PCNA. It also regulates the activity and protein expression of the DA transporter (DAT) through the activation of RhoA. In response to H2O2 treatment, MAPK15 phosphorylates ELAVL1, preventing it from binding to the PDCD4 3'UTR. This makes the PDCD4 mRNA accessible to miR-21, leading to its degradation and loss of protein expression. MAPK15 also functions in a kinase activity-independent manner as a negative regulator of growth. It has been shown to phosphorylate FOS and MBP in vitro. During oocyte maturation, MAPK15 plays a key role in microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos. It interacts with ESRRA, promoting its re-localization from the nucleus to the cytoplasm and inhibiting its transcriptional activity. MAPK15 also interacts with CSK/c-Src, ABL1, RET, and TGFB1I1. It interacts with GABARAP, MAP1LC3B, and GABARAPL1, controlling both basal and starvation-induced autophagy in a kinase-dependent manner. It also interacts with ESRRA, promoting its re-localization to the cytoplasm through a XPO1-dependent mechanism and inhibiting its transcriptional activity. The interaction between MAPK15 and PCNA, which is dependent on chromatin binding and kinase activity, prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2. MAPK15 also interacts with DVL2 and CLIC3, although it does not phosphorylate CLIC3.

MAPK15 is also known as ERK7, ERK8.

Associated Diseases

WES Whole Exome Sequencing