Glycogen synthase kinase-3 - An overview of an over-achieving protein kinase

被引:238
作者
Kockeritz, Lisa
Doble, Bradley
Patel, Satish
Woodgett, James R.
机构
[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[2] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada
关键词
D O I
10.2174/1389450110607011377
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Glycogen synthase kinase-3 (GSK-3) has attracted much scrutiny due to its plethora of cellular functions, novel mechanisms of regulation and its potential as a therapeutic target for several common diseases. In mammals, GSK-3 is encoded by two genes, termed GSK-3 alpha and GSK-3 beta, that yield related but distinct protein-serine kinases. GSK-3 is unusual in that its protein kinase activity tends to be high in resting cells and cellular stimuli, such as hormones and growth factors, result in its catalytic inactivation. Further, many of the substrate proteins of GSK-3 are functionally inhibited by phosphorylation. Thus, signals that inhibit GSK-3 often cause activation of its diverse array of target proteins. Regulation of GSK-3 is important for normal development, regulation of metabolism, neuronal growth and differentiation and modulation of cell death. Dysregulation of GSK-3 activity has been implicated in human pathologies such as neurodegenerative diseases and type-2 diabetes. In this introductory chapter we provide a primer on the modes of GSK-3 regulation and a description of the various signaling pathways and cellular processes in which GSK-3 is an active participant.
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页码:1377 / 1388
页数:12
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