Dual specificity phosphatases: a gene family for control of MAP kinase function

Mitogen-activated protein (MAP) kinases are important players in signal tra nsduction pathways activated by a range of stimuli and mediate a number of physiological and pathological changes in cell function. MAP kinase activat ion requires phosphorylation on a threonine and tyrosine residue located wi thin the activation loop of kinase subdomain VIII, This process is reversib le even in the continued presence of activating stimuli, indicating that pr otein phosphatases provide an important mechanism for MAP kinase control. D ual 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 re sidues 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 i s 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 exp ression is induced strongly by various growth factors and/or cellular stres ses, providing a sophisticated transcriptional mechanism for targeted inact ivation of selected MAP kinase activities.-Camps, M., Nichols, A., Arkinsta ll, S, Dual specificity phosphatases: a gene family for control of MAP kina se function.