MKP-1/p38 Active Protein

The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protein with structural features similar to members of the non-receptor-type protein-tyrosine phosphatase family, and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The bacterially expressed and purified DUSP1 protein has intrinsic phosphatase activity, and specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation of both its phosphothreonine and phosphotyrosine residues. Furthermore, it suppresses the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, DUSP1 may play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. [provided by RefSeq, Jul 2008]

MKP-1: a non-receptor, dual-specificity phosphoprotein phosphatase (DUSP). Different members of the DUSP family show distinct substrate specificities for MAPKs, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. DUSP1 specifically inactivates mitogen-activated protein (MAP) kinase in vitro by the concomitant dephosphorylation. It is induced in human skin fibroblasts by oxidative/heat stress and growth factors. Contains 1 rhodanese domain.

Protein type: EC 3.1.3.16; Motility/polarity/chemotaxis; EC 3.1.3.48; Protein phosphatase, dual-specificity

Chromosomal Location of Human Ortholog: 5q34

Cellular Component: cytoplasm; nucleus

Molecular Function: protein tyrosine/threonine phosphatase activity; protein binding; protein tyrosine/serine/threonine phosphatase activity; non-membrane spanning protein tyrosine phosphatase activity; MAP kinase tyrosine/serine/threonine phosphatase activity

Biological Process: response to light stimulus; negative regulation of MAP kinase activity; response to cAMP; response to retinoic acid; negative regulation of MAPKKK cascade; positive regulation of apoptosis; response to glucocorticoid stimulus; negative regulation of meiotic cell cycle; response to testosterone stimulus; protein amino acid dephosphorylation; response to estradiol stimulus; cellular response to hormone stimulus; regulation of apoptosis; response to hydrogen peroxide; endoderm formation; response to oxidative stress; response to calcium ion; negative regulation of apoptosis; inactivation of MAPK activity