Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain.
Axin is a negative regulator of embryonic axis formation in vertebrates, which acts through a Wnt signal transduction pathway involving the serine/threonine kinase GSK-3 and beta-catenin. Axin has been shown to have distinct binding sites for GSK-3 and beta-catenin and to promote the phosphorylation of beta-catenin and its consequent degradation. ... This provides an explanation for the ability of Axin to inhibit signaling through beta-catenin. In addition, a more N-terminal region of Axin binds to adenomatous polyposis coli (APC), a tumor suppressor protein that also regulates levels of beta-catenin. Here, we report the results of a yeast two-hybrid screen for proteins that interact with the C-terminal third of Axin, a region in which no binding sites for other proteins have previously been identified. We found that Axin can bind to the catalytic subunit of the serine/threonine protein phosphatase 2A through a domain between amino acids 632 and 836. This interaction was confirmed by in vitro binding studies as well as by co-immunoprecipitation of epitope-tagged proteins expressed in cultured cells. Our results suggest that protein phosphatase 2A might interact with the Axin.APC.GSK-3.beta-catenin complex, where it could modulate the effect of GSK-3 on beta-catenin or other proteins in the complex. We also identified a region of Axin that may allow it to form dimers or multimers. Through two-hybrid and co-immunoprecipitation studies, we demonstrated that the C-terminal 100 amino acids of Axin could bind to the same region as other Axin molecules.
Mesh Terms:
Cell Line, Humans, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphorylation, Precipitin Tests, Protein Binding, Protein Phosphatase 2, Proteins, Repressor Proteins
Cell Line, Humans, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphorylation, Precipitin Tests, Protein Binding, Protein Phosphatase 2, Proteins, Repressor Proteins
J. Biol. Chem.
Date: Feb. 05, 1999
PubMed ID: 9920888
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