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Báo cáo Y học: Regulation of stress-activated protein kinase signaling pathways by protein phosphatases

Stress-activated protein kinase (SAPK) signaling plays essential roles in eliciting adequate cellular responses to stresses and proinflammatory cytokines. SAPK pathways are composed of three successive protein kinase reactions. The phosphorylation of SAPK signaling components on Ser/Thr or Thr/Tyr residues suggests the involvement of various protein phosphatases in the negative regulation of these systems. Accumulating evidence indicates that three families of protein phosphatases, namely the Ser/Thr phosphatases, the Tyr phosphatases and the dual specif- icity Ser/Thr/Tyr phosphatases regulate these pathways, each mediating a distinct function | Eur. J. Biochem. 269 1060-1066 2002 FEBS 2002 MINIREVIEW Regulation of stress-activated protein kinase signaling pathways by protein phosphatases Shinri Tamura Masahito Hanada Motoko Ohnishi Koji Katsura Masato Sasaki and Takayasu Kobayashi Department of Biochemistry Institute of Development Aging and Cancer Tohoku University Aoba-ku Sendai Japan Stress-activated protein kinase SAPK signaling plays essential roles in eliciting adequate cellular responses to stresses and proinflammatory cytokines. SAPK pathways are composed of three successive protein kinase reactions. The phosphorylation of SAPK signaling components on Ser Thr or Thr Tyr residues suggests the involvement of various protein phosphatases in the negative regulation of these systems. Accumulating evidence indicates that three families of protein phosphatases namely the Ser Thr phosphatases the Tyr phosphatases and the dual specif icity Ser Thr Tyr phosphatases regulate these pathways each mediating a distinct function. Differences in substrate specificities and regulatory mechanisms for these phosphatases form the molecular basis for the complex regulation of SAPK signaling. Here we describe the properties of the protein phosphatases responsible for the regulation of SAPK signaling pathways. Keywords stress response stress-activated protein kinase protein phosphatase. INTRODUCTION Stress-activated protein kinases SAPKs a subfamily of the mitogen-activated protein kinase MAPK superfamily are highly conserved from yeast to mammals. SAPKs relay signals in response to various extracellular stimuli including environmental stresses and proinflammatory cytokines. In mammalian cells two distinct classes of SAPKs have been identified the c-Jun N-terminal kinases JNK and the p38 MAPKs 1 2 Fig. 1 . The activation of SAPKs requires phosphorylation of conserved tyrosine and threonine residues within the catalytic domain. This phosphorylation is mediated by dual specificity protein kinases members of the MAPK kinase