MAPK12

Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq]

mitogen-activated protein kinase 12

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration.

Cell cycleIEA:UniProtKB-KW
DNA damage induced protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
MAPK cascadeTAS:Reactome
Muscle organ developmentManual Assertion Based On ExperimentTAS:ProtInc
Myoblast differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell cycleIEA:Ensembl
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of muscle cell differentiationTAS:Reactome
Positive regulation of peptidase activity1 PublicationNAS:ParkinsonsUK-UCL
Regulation of cell cycleManual Assertion Based On ExperimentTAS:ProtInc
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Nucleus
Mitochondrion
Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma (By similarity).

MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.

Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.
Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway.