Diverse physiological functions for dual-specificity MAP kinase phosphatases

被引:281
作者
Dickinson, Robin J. [1 ]
Keyse, Stephen M. [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Canc Res UK Stress Response Lab, Dundee DD1 9SY, Scotland
关键词
MAPK; MKP; signal transduction; phosphorylation;
D O I
10.1242/jcs.03266
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A structurally distinct subfamily of ten dual-specificity (Thr/Tyr) protein phosphatases is responsible for the regulated dephosphorylation and inactivation of mitogen-activated protein kinase ( MAPK) family members in mammals. These MAPK phosphatases (MKPs) interact specifically with their substrates through a modular kinase-interaction motif (KIM) located within the N-terminal noncatalytic domain of the protein. In addition, MAPK binding is often accompanied by enzymatic activation of the C-terminal catalytic domain, thus ensuring specificity of action. Despite our knowledge of the biochemical and structural basis for the catalytic mechanism of the MKPs, we know much less about their regulation and physiological functions in mammalian cells and tissues. However, recent studies employing a range of model systems have begun to reveal essential non-redundant roles for the MKPs in determining the outcome of MAPK signalling in a variety of physiological contexts. These include development, immune system function, metabolic homeostasis and the regulation of cellular stress responses. Interestingly, these functions may reflect both restricted subcellular MKP activity and changes in the levels of signalling through multiple MAPK pathways.
引用
收藏
页码:4607 / 4615
页数:9
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