MAPK7
Description
The MAPK7 (mitogen-activated protein kinase 7) is a protein-coding gene located on chromosome 17.
Mitogen-activated protein kinase 7, also known as MAP kinase 7, is an enzyme that in humans is encoded by the MAPK7 gene. MAPK7 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 is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled receptors. In response to extracellular signals, this kinase translocates to the cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. MAPK7 is also critical for cardiovascular development and is essential for endothelial cell function. MAPK7 has been shown to interact with: XMD8-92 was one of the first described ERK5 inhibitors and was used in several pharmacological studies as tool compound. However, XMD8-92 hits BRD4 as an off-target leading to false or inconclusive results.
MAPK7 plays a crucial role in various cellular processes, including proliferation, differentiation, and cell survival. It is activated by the MAPK kinase MAP2K5, leading to its translocation to the nucleus where it phosphorylates downstream targets like MEF2C. Notably, EGF activates MAPK7 via a Ras-independent pathway that depends on MAP2K5. As part of the MAPK/ERK signaling pathway, MAPK7 functions as a negative regulator of apoptosis in cardiomyocytes by interacting with STUB1/CHIP and promoting STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM. MAPK7 may be involved in muscle cell differentiation and is potentially important for endothelial function and the maintenance of blood vessel integrity. MAPK7 interacts specifically with MAP2K5, but not with MEK1/ERK1 or MEK2/ERK2 pathways. MAPK7 phosphorylates SGK1 at Ser-78, which is required for growth factor-induced cell cycle progression. Furthermore, MAPK7 regulates p53/TP53 by disrupting the PML-MDM2 interaction.
MAPK7 is also known as BMK1, ERK4, ERK5, PRKM7.
