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MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Yao R,Natsume Y,Noda T

doi

10.1038/sj.onc.1207817

subject

Has Abstract

pub_date

2004-08-12 00:00:00

pages

6023-30

issue

36

eissn

0950-9232

issn

1476-5594

pii

1207817

journal_volume

23

pub_type

杂志文章

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