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  • Original Paper
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GSK-3β-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by β-catenin and protein phosphatase 2A complexed with Axin

Oncogene volume 19, pages 537–545 (2000)Cite this article

Abstract

Axin forms a complex with adenomatous polyposis coli gene product (APC), glycogen synthase kinase-3β (GSK-3β), and β-catenin through different binding sites and downregulates β-catenin. GSK-3β-dependent phosphorylation of APC-(1211-2075) which has the Axin-binding site was facilitated by Axin, but that of APC-(959-1338) which lacks the Axin-binding site was not. Axin-(298-506) or Axin-(298-832), which has the GSK-3β- and β-catenin- but not APC-binding sites, did not enhance GSK-3β-dependent phosphorylation of either APC-(1211-2075) or APC-(959-1338). Furthermore, β-catenin stimulated the phosphorylation of APC-(959-1338) and APC-(1211-2075) by GSK-3β in the presence of Axin. Consistent with these in vitro observations, expression of β-catenin or Axin in COS cells promoted an SDS gel band shift of APC. These results indicate that APC complexed with Axin is effectively phosphorylated by GSK-3β and that β-catenin may modulate this phosphorylation. In addition, the heterodimeric form of protein phosphatase 2A (PP2A) directly bound to Axin, and PP2A complexed with Axin dephosphorylated APC phosphorylated by GSK-3β. Taken together, these results suggest that GSK-3β-dependent phosphorylation of APC can be modulated by β-catenin and PP2A complexed with Axin.

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Acknowledgements

We thank Dr M Takeda for helpful discussion and critical reading of the manuscript. We are grateful to Drs JR Woodgett, T Akiyama, A Nagafuchi, CW Turck, M Nakata, and K Yonezawa for providing plasmids, peptides, and antibodies. 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, Japan (1998, 1999), and by grants from the Yamanouchi Foundation for Research on Metabolic Disorders (1998), and Uehara Memorial Foundation (1998). We wish to thank the Research Center for Molecular Medicine, Hiroshima University School of Medicine, for the use of their facilities.

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  1. Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Satoshi Ikeda, Michiko Kishida, Hirofumi Usui & Akira Kikuchi

  2. Department of Virology II, National Institute of Infectious Disease, 1-23-1, Toyama, Shinjuku-ku, 162-8640, Tokyo, Japan

    Yoshiharu Matsuura

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Ikeda, S., Kishida, M., Matsuura, Y. et al. GSK-3β-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by β-catenin and protein phosphatase 2A complexed with Axin. Oncogene 19, 537–545 (2000). https://doi.org/10.1038/sj.onc.1203359

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