Premium
A GSK3‐binding peptide from FRAT1 selectively inhibits the GSK3‐catalysed phosphorylation of Axin and β‐catenin
Author(s) -
Thomas Gareth M.,
Frame Sheelagh,
Goedert Michel,
Nathke Inke,
Polakis Paul,
Cohen Philip
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01161-8
Subject(s) - gsk 3 , phosphorylation , catenin , microbiology and biotechnology , gsk3b , xenopus , biology , glycogen synthase , chemistry , beta catenin , kinase , wnt signaling pathway , biochemistry , signal transduction , gene
The Axin‐dependent phosphorylation of β‐catenin catalysed by glycogen synthase kinase‐3 (GSK3) is inhibited during embryogenesis. This protects β‐catenin against ubiquitin‐dependent proteolysis, leading to its accumulation in the nucleus, where it controls the expression of genes important for development. Frequently rearranged in advanced T‐cell lymphomas 1 (FRAT1) is a mammalian homologue of a GSK3‐binding protein (GBP), which appears to play a key role in the correct establishment of the dorsal‐ventral axis in Xenopus laevis . Here, we demonstrate that FRATtide (a peptide corresponding to residues 188–226 of FRAT1) binds to GSK3 and prevents GSK3 from interacting with Axin. FRATtide also blocks the GSK3‐catalysed phosphorylation of Axin and β‐catenin, suggesting a potential mechanism by which GBP could trigger axis formation. In contrast, FRATtide does not suppress GSK3 activity towards other substrates, such as glycogen synthase and eIF2B, whose phosphorylation is independent of Axin but dependent on a ‘priming’ phosphorylation. This may explain how the essential cellular functions of GSK3 can continue, despite the suppression of β‐catenin phosphorylation.