Document Detail

Identification of the Axin and Frat binding region of glycogen synthase kinase-3.
MedLine Citation:
PMID:  11707456     Owner:  NLM     Status:  MEDLINE    
Glycogen synthase kinase-3 (GSK-3) is a key component of several signaling pathways including those regulated by Wnt and insulin ligands. Specificity in GSK-3 signaling is thought to involve interactions with scaffold proteins that localize GSK-3 regulators and substrates. This report shows that GSK-3 forms a low affinity homodimer that is disrupted by binding to Axin and Frat. Based on the crystal structure of GSK-3, we have used surface-scanning mutagenesis to identify residues that differentially affect GSK-3 interactions. Mutations that disrupt Frat and Axin cluster at the dimer interface explaining their effect on homodimer formation. Loss of the Axin binding site blocks the ability of dominant negative GSK-3 to cause axis duplication in Xenopus embryos. The Axin binding site is conserved within all GSK-3 proteins, and its loss affects both cell motility and gene expression in the nonmetazoan, Dictyostelium. Surprisingly, we find no genetic interaction between a non-Axin-binding GSK-3 mutant and T-cell factor activity, arguing that Axin interactions alone cannot explain the regulation of T-cell factor-mediated gene expression.
Elizabeth Fraser; Neville Young; Rana Dajani; Jonathan Franca-Koh; Jonathan Ryves; Robin S B Williams; Margaret Yeo; Marie-Therese Webster; Chris Richardson; Matthew J Smalley; Laurence H Pearl; Adrian Harwood; Trevor C Dale
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-11-13
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-14     Completed Date:  2002-02-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2176-85     Citation Subset:  IM    
Cancer Research Campaign Centre for Cell and Molecular Biology and Section of Structural Biology, Institute of Cancer Research, 237 Fulham Rd., London SW3 6JB, United Kingdom.
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MeSH Terms
Amino Acid Substitution
Binding Sites
Calcium-Calmodulin-Dependent Protein Kinases / chemistry,  genetics,  metabolism*
Carrier Proteins*
Cell Line
Crystallography, X-Ray
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Intracellular Signaling Peptides and Proteins
Models, Molecular
Neoplasm Proteins*
Protein Conformation
Proteins / metabolism*
Proto-Oncogene Proteins / metabolism*
Repressor Proteins*
Xenopus Proteins*
Reg. No./Substance:
0/Axin protein; 0/Carrier Proteins; 0/FRAT1 protein, human; 0/GBP protein, Xenopus; 0/Intracellular Signaling Peptides and Proteins; 0/Neoplasm Proteins; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Xenopus Proteins; EC 2.7.11.-/Glycogen Synthase Kinases; EC Protein Kinases; EC Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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