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PMID: 15494020 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Glycogen synthase kinase-3 in insulin and Wnt signalling: a double-edged sword?

Biochemical Society transactions ·Vol. 32 ·No. Pt 5 ·2004-11-00 ·Pages 803-8

Patel S, Doble B, Woodgett JR

Abstract

Glycogen synthase kinase-3 is an unusual protein serine/threonine kinase that, unlike most of its 500-odd relatives in the genome, is active under resting conditions and is inactivated upon cell stimulation. The two mammalian isoforms, GSK-3alpha and beta, play largely overlapping roles and have been implicated in a variety of human pathologies, including Type II diabetes, Alzheimer's disease, bipolar disorder and cancer. Recently, the modes of regulation of this enzyme have been elucidated through a combination of structural and cell biological studies. A series of relatively selective small molecules have facilitated chemical manipulation of the enzyme in intact cells and tissues, and new roles for the protein kinase in embryonic stem cell differentiation and motility have emerged. Despite these advances, the therapeutic value of this enzyme as a drug target remains clouded by uncertainty over the potential of antagonists to promote tumorigenesis. This article describes the state of understanding of this intriguing enzyme, and weighs current evidence regarding whether there is a therapeutic window for amelioration of diseases in which it is implicated, in the absence of inducing new pathologies.

MeSH Terms
Animals Cell Differentiation Cell Movement Enzyme Activation Glycogen/metabolism Glycogen Synthase Kinase 3/metabolism,physiology Humans Insulin/metabolism Intercellular Signaling Peptides and Proteins/metabolism Models, Biological Mutation Neoplasms/metabolism Phosphorylation Protein Binding Protein Isoforms Signal Transduction Wnt Proteins
Chemicals
Insulin Intercellular Signaling Peptides and Proteins Protein Isoforms Wnt Proteins Glycogen Glycogen Synthase Kinase 3
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Patel S
Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
Doble B
Woodgett J R
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Article Info
Journal
Biochemical Society transactions
Abbr.
Biochem Soc Trans
ISSN
0300-5127
DOI
10.1042/BST0320803
Published
2004-11-00
Pages
803-8
Language
English
Region
England
NLM ID
7506897
PMCID
PMC4485494
Subset
IM
Grants
Canadian Institutes of Health Research · 12043 · Canada
External Links
PubMed source DOI: 10.1042/BST0320803 PMC Full Text View journal details
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