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
Current Drug Targets
Title: Glycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase
Volume: 7 Issue: 11
Author(s): Lisa Kockeritz, Bradley Doble, Satish Patel and James R. Woodgett
Affiliation:
Keywords: autophosphorylation, Wnt signaling, GSK-3 binding protein, Xenopus embryos, Hedgehog (Hh) ligand
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.
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Cite this article as:
Kockeritz Lisa, Doble Bradley, Patel Satish and Woodgett R. James, Glycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase, Current Drug Targets 2006; 7 (11) . https://dx.doi.org/10.2174/1389450110607011377
DOI https://dx.doi.org/10.2174/1389450110607011377 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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