Fraser, Elizabeth, Young, N., Dajani, R., Franca-Koh, J., Ryves, William Jonathan, Williams, R. S. B., Yeo, M., Webster, M.-T., Richardson, C., Smalley, Matthew John  ORCID: https://orcid.org/0000-0001-9540-1146, Pearl, L. H., Harwood, Adrian John ORCID: https://orcid.org/0000-0003-3124-5169 and Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963
2002.
Identification of the Axin and Frat binding region of glycogen synthase kinase-3.
Journal of Biological Chemistry
277
(3)
, pp. 2176-2185.
10.1074/jbc.M109462200
|
Abstract
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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) Research Institutes & Centres > European Cancer Stem Cell Research Institute (ECSCRI) |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history > QH301 Biology |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| ISSN: | 0021-9258 |
| Last Modified: | 22 Jun 2023 10:01 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/46400 |
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