MAPK1 gene

The MAPK1 gene (MAPK1 stands for: mitogen-activated protein kinase 1) is a protein-coding gene located on chromosome 22q11.22. Two alternatively spliced transcript variants have been reported for this gene, which code for the same protein but differ in the untranslated regions (UTRs).

This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as integration points for multiple biochemical signals and are involved in a variety of cellular processes including proliferation, differentiation, transcriptional regulation, and development.

Activation of this kinase requires its phosphorylation by upstream kinases.

Upon activation, this kinase migrates to the nucleus of stimulated cells where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been termed a "moonlighting protein" because of its ability to perform mechanistically distinct functions.

MAPK1/ERK2 and MAPK3/ERK1 are the two MAPKs that play important roles in the MAPK/ERK cascade. They are also involved in a signaling cascade triggered by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates various biological functions such as cell growth, adhesion, survival, and differentiation by regulating transcription, translation, and cytoskeleton rearrangement. The MAPK/ERK cascade also plays a role in the initiation and regulation of meiosis, mitosis, and post-mitotic functions in differentiated cells by phosphorylating a number of transcription factors. Approximately 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus and appear to participate in the regulation of transcription after stimulation. However, other substrates are located in the cytosol as well as in other cell organelles and are responsible for processes such as translation, mitosis, and apoptosis. In addition, the MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as fragmentation of the Golgi apparatus during mitosis.

Substrates include.

• Transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4, or SPZ1).
• elements of the cytoskeleton (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1)
• regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG)
• Translational regulators (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules.

Diseases associated with MAPK1 include Noonan syndrome 13

and

specific learning disability.