Axin, a Negative Regulator of the Wnt Signaling Pathway, Directly Interacts with Adenomatous Polyposis Coli and Regulates the Stabilization of β-Catenin*
- Shosei Kishida,
- Hideki Yamamoto,
- Satoshi Ikeda,
- Michiko Kishida,
- Ikuo Sakamoto,
- Shinya Koyama and
- Akira Kikuchi‡
- From the Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract
The regulators of G protein signaling (RGS) domain of Axin, a negative regulator of the Wnt signaling pathway, made a complex with full-length adenomatous polyposis coli (APC) in COS, 293, and L cells but not with truncated APC in SW480 or DLD-1 cells. The RGS domain directly interacted with the region containing the 20-amino acid repeats but not with that containing the 15-amino acid repeats of APC, although both regions are known to bind to β-catenin. In the region containing seven 20-amino acid repeats, the region containing the latter five repeats bound to the RGS domain of Axin. Axin and β-catenin simultaneously interacted with APC. Furthermore, Axin stimulated the degradation of β-catenin in COS cells. Taken together with our recent observations that Axin directly interacts with glycogen synthase kinase-3β (GSK-3β) and β-catenin and that it promotes GSK-3β-dependent phosphorylation of β-catenin, these results suggest that Axin, APC, GSK-3β, and β-catenin make a tetrameric complex, resulting in the regulation of the stabilization of β-catenin.
Footnotes
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↵* This work was supported by grants-in-aid for scientific research and for scientific research on priority areas from the Ministry of Education, Science, and Culture of Japan (1997) and by grants from the Yamanouchi Foundation for Research on Metabolic Disorders (1997), the Kato Memorial Bioscience Foundation (1997), and the Naito Foundation (1997).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 81-82-257-5130; Fax: 81-82-257-5134; E-mail: akikuchi{at}mcai.med.hiroshima-u.ac.jp.
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↵1 The abbreviations used are: GSK-3β, glycogen synthase kinase-3β; APC, adenomatous polyposis coli; FAP, familial adenomatous polyposis; aa, amino acid(s); RGS, regulators of G protein signaling; G protein, GTP-binding protein; GST, glutathioneS-transferase; MBP, maltose-binding protein; HA, hemagglutinin.
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- Received December 16, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
