title: Dual specificity phosphatases: a gene family for control of MAP kinase function.
abstract: Mitogen-activated protein (MAP) kinases are important players in signal transduction pathways activated by a range of stimuli and mediate a number of physiological and pathological changes in cell function. MAP kinase activation requires phosphorylation on a threonine and tyrosine residue located within the activation loop of kinase subdomain VIII. This process is reversible even in the continued presence of activating stimuli, indicating that protein phosphatases provide an important mechanism for MAP kinase control. Dual specificity phosphatases (DSPs) are an emerging subclass of the protein tyrosine phosphatase (PTP) gene superfamily, which appears to be selective for dephosphorylating the critical phosphothreonine and phosphotyrosine residues within MAP kinases. Some DSPs are localized to different subcellular compartments and moreover, certain family members appear highly selective for inactivating distinct MAP kinase isoforms. This enzymatic specificity is due in part to powerful catalytic activation of the DSP phosphatase after tight binding of its amino-terminal to the target MAP kinase. DSP gene expression is induced strongly by various growth factors and/or cellular stresses, providing a sophisticated transcriptional mechanism for targeted inactivation of selected MAP kinase activities.
authors.affiliation: Serono Pharmaceutical Research Institute, Ares-Serono International SA, 1228 Plan-les-Ouates, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Camps
authors.forename: A
authors.initials: A
authors.lastname: Nichols
authors.forename: S
authors.initials: S
authors.lastname: Arkinstall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases