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Threonine 41 in β-Catenin Serves as a Key Phosphorylation Relay Residue in β-Catenin Degradation.
- Source :
-
Biochemistry . 4/25/2006, Vol. 45 Issue 16, p5319-5323. 5p. 7 Diagrams. - Publication Year :
- 2006
-
Abstract
- β-Catenin phosphorylation at serine 45 (Ser45), threonine 41 (Thr41), Ser37, and Ser33 is critical for β-catenin degradation, and regulation of β-catenin phosphorylation is a central part of the canonical Wnt signaling pathway. β-Catenin mutations at Ser45, Thr41, Ser37, and Ser33 perturb β-catenin degradation and are frequently found in cancers. It is established that Ser45 phosphorylation by casein kinase I (CKI) initiates phosphorylation at Thr41, Ser37, and Ser33 by glycogen synthase kinase 3 (GSK3) and that phosphorylated Ser37 and Ser33 are recognized by the F-box protein β-TrCP, a component of a ubiquitin ligase complex that mediates β-catenin degradation. While the roles of Set45, Ser37, and Ser33 are well documented, the function of Thr41 remains less defined. Here we show that Thr41 strictly acts as a phosphorylation relay residue and that the Ser-X-X-X-Ser (X is any amino acid) motif is obligatory for β-catenin phosphorylation by GSK3. β-Catenin phosphorylation/degradation and its regulation by Wnt can occur normally in the absence of Thr41 as long as the Ser-X-X-X-Ser motif/spacing is preserved. These results suggest that Thr41 functions to bridge sequential phosphorylation from Ser45 to Ser37 and provide further insights into the discrete steps and logic in β-catenin phosphorylation-degradation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062960
- Volume :
- 45
- Issue :
- 16
- Database :
- Academic Search Index
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20778551
- Full Text :
- https://doi.org/10.1021/bi0601149