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GSKIP Is Homologous to the Axin GSK3β Interaction Domain and Functions as a Negative Regulator of GSK3β.
- Source :
-
Biochemistry . 9/26/2006, Vol. 45 Issue 38, p11379-11389. 11p. 6 Diagrams, 1 Graph. - Publication Year :
- 2006
-
Abstract
- Although prominent FRAT/GBP exhibits a limited degree of homology to Axin, the binding sites on GSK3 for FRAT/GBP and Axin may overlap to prevent the effect of FRAT/GBP in stabilizing β-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3β interaction protein (GSKIP), which binds to GSK3β. We have defined a 25-amino acid region in the C-terminus of GSKIP that is highly similar to the GSK3β interaction domain (GID) of Axin. Using an in vitro kinase assay, our results indicate that GSKIP is a good GSK3β substrate, and both the full-length protein and a C-terminal fragment of GSKIP can block phosphorylation of primed and nonprimed substrates in different fashions. Similar to Axin GID381–405 and FRATtide, synthesized GSKIPtide is also shown to compete with and/or block the phosphorylation of Axin and β-catenin by GSK3β. Furthermore, our data indicate that overexpression of GSKIP induces β-catenin accumulation in the cytoplasm and nucleus as visualized by immunofluorescence. A functional assay also demonstrates that GSKIP-transfected cells have a significant effect on the transactivity of Tcf-4. Collectively, we define GSKIP as a naturally occurring protein that is homologous with the GSK3β interaction domain of Axin and is able to negatively regulate GSK3β of the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062960
- Volume :
- 45
- Issue :
- 38
- Database :
- Academic Search Index
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22563683
- Full Text :
- https://doi.org/10.1021/bi061147r