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Link to original content: https://doi.org/10.1038/sj.onc.1207817
MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap | Oncogene
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MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap

Oncogene volume 23, pages 6023–6030 (2004)Cite this article

Abstract

A seven-transmembrane protein, frizzled, has been implicated in a planar cell polarity (PCP) pathway as well as the canonical Wnt signaling pathway. Although both pathways require a cytoplasmic protein, dishevelled, the molecular mechanism by which frizzled regulates intracellular signaling remains to be elucidated. In the mouse, nine frizzled family members have been identified and six of them contain a PDZ-binding motif at their carboxyl-termini. In this study, we show that a multi-PDZ containing protein, MAGI-3, specifically binds to frizzled-4 and -7. Furthermore, we also demonstrate that MAGI-3 interacts with Ltap, a mouse homolog of the Drosophila PCP protein, stbm, and that these three molecules can form a ternary complex. In epithelial cells, MAGI-3, frizzled-4, and Ltap colocalized at cell contact sites, indicating that these molecules form a physiologically significant complex. Finally, we found that MAGI-3 strongly activated JNK in conjunction with frizzled-4 and Ltap, and that this activation required the small GTPase, Rac. These results indicate that MAGI-3 functions as a scaffold protein for frizzled-4 and Ltap and regulates the JNK signaling cascade.

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Acknowledgements

We thank Dr E Peles for MAGI-3 cDNA and antibody. We also thank Drs A Hall, J Nathans, T Sudo, Y Kasuya, A Kikuchi, and J Miyazaki for plasmids. This work was supported by a Grant-Aid for Scientific Research from the Ministry on Education, Sports, Science, and Culture of Japan.

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Authors and Affiliations

  1. Department of Cell Biology, The JFCR-Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan

    Ryoji Yao, Yasuko Natsume & Tetsuo Noda

  2. Center for Translational Advanced Animal Research for Human Diseases, Tohoku University School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan

    Tetsuo Noda

  3. Mouse Functional Genomic Research Group, RIKEN Genomic Science Center, 214 Maeda-cho, Totsuka-ku, Yokohama, 244-0804, Kanagawa, Japan

    Tetsuo Noda

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  1. Ryoji Yao
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Correspondence to Tetsuo Noda.

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Yao, R., Natsume, Y. & Noda, T. MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap. Oncogene 23, 6023–6030 (2004). https://doi.org/10.1038/sj.onc.1207817

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