Mitogen-activated protein kinase phosphatase: a negative regulator of the mitogen-activated protein kinase cascade

Mitogen-activated protein kinases (MAPKs) are activated by various stimuli, such as growth factors, cytokines, or stress, and are considered to be imp ortant mediators in intracellular signal transduction networks. The dual-sp ecificity kinases, MAPK kinases (MKKs), which phosphorylate the TXY motif i n the catalytic domain of MAPKs, can cause the activation of MAPKs. Recentl y, a family of dual-specificity phosphatases has been identified, members o f which are able to dephosphorylate and inactivate MAPKs. The studies cited in this review have revealed that these MAPK phosphatases might play an im portant role in various cellular functions by downregulating the MAPK casca de. (C) 1999 Elsevier Science B.V. All rights reserved.