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Molecular and Cellular Biology, January 2001, p. 330-342, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.330-342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

Shin-ichiro Hino,1 Shosei Kishida,1,2 Tatsuo Michiue,3 Akimasa Fukui,4 Ikuo Sakamoto,1 Shinji Takada,5,6 Makoto Asashima,3,4 and Akira Kikuchi1,*

Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551,1 PRESTO, Japan Science and Technology Corporation, Hiroshima,2 Crest Project3 and Department of Life Science (Biology),4 University of Tokyo, Meguro-ku, Tokyo 153-8902, and Center for Molecular and Developmental Biology, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502,5 and Kondoh Differentiation Signaling Project, ERATO, Japan Science and Technology Corporation, Kyoto,6 Japan

Received 5 June 2000/Returned for modification 6 July 2000/Accepted 12 October 2000

In attempting to clarify the roles of Dvl in the Wnt signaling pathway, we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl. Immunocytochemical analyses showed that Idax was localized to the same place as Dvl in cells and that expression of Axin inhibited the colocalization of Dvl and Idax. Further, Wnt-induced accumulation of beta -catenin and activation of T-cell factor in mammalian cells were suppressed by expression of Idax. Expression of Idax in Xenopus embryos induced ventralization with a reduction in the expression of siamois, a Wnt-inducible gene. Idax inhibited Wnt- and Dvl- but not beta -catenin-induced axis duplication. It is known that Dvl is a positive regulator in the Wnt signaling pathway and that the PDZ domain is important for this activity. Therefore, these results suggest that Idax functions as a negative regulator of the Wnt signaling pathway by directly binding to the PDZ domain of Dvl.

* Corresponding author. Mailing address: Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Phone: 81-82-257-5130. Fax: 81-82-257-5134. E-mail: akikuchi{at}mcai.med.hiroshima-u.ac.jp.

Molecular and Cellular Biology, January 2001, p. 330-342, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.330-342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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