Responds to activation by environmental stress, pro-inflammatory cytokines and lipopolysaccharide (LPS) by phosphorylating a number of transcription factors, such as ELK1 and ATF2 and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. Plays a critical role in the production of some cytokines, for example IL-6. May play a role in stabilization of EPO mRNA during hypoxic stress. Isoform Mxi2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform Exip may play a role in the early onset of apoptosis.
Brain, heart, placenta, pancreas and skeletal muscle. Expressed to a lesser extent in lung, liver and kidney.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Dually phosphorylated on Thr-180 and Tyr-182, which activates the enzyme. Phosphorylated upon DNA damage, probably by ATM or ATR.
Zhou W et al. MicroRNA-138 inhibits hypoxia-induced proliferation of endothelial progenitor cells via inhibition of HIF-1a-mediated MAPK and AKT signaling. Exp Ther Med13:1017-1024 (2017).
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