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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 7
ISSUE: 11
DOI: 10.2174/1389450110607011377      Price:  $58









Glycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase

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Author(s): Lisa Kockeritz, Bradley Doble, Satish Patel and James R. Woodgett
Pages 1377-1388 (12)
Abstract:
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-3α and GSK-3β, 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.
Keywords:
autophosphorylation, Wnt signaling, GSK-3 binding protein, Xenopus embryos, Hedgehog (Hh) ligand
Affiliation:
Samuel Lunenfeld Research Institute, 600 University Avenue, Ontario M5G 1X5, Canada.