QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 10, 2008
doi: 10.1242/10.1242/jcs.021964

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bikkavilli, R. K. Articles by Malbon, C. C. Search for Related Content PubMed Articles by Bikkavilli, R. K. Articles by Malbon, C. C.

G_o mediates WNT-JNK signaling through Dishevelled 1 and 3, RhoA family members, and MEKK 1 and 4 in mammalian cells

Department of Pharmacology, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA

^* Author for correspondence (e-mail: kamesh{at}pharm.stonybrook.edu)

Accepted 23 October 2007

In Drosophila, activation of Jun N-terminal Kinase (JNK) mediated by Frizzled and Dishevelled leads to signaling linked to planar cell polarity. A biochemical delineation of WNT-JNK planar cell polarity was sought in mammalian cells, making use of totipotent mouse F9 teratocarcinoma cells that respond to WNT3a via Frizzled-1. The canonical WNT–β-catenin signaling pathway requires both G_o and G_q heterotrimeric G-proteins, whereas we show that WNT-JNK signaling requires only G_o protein. G_o propagates the signal downstream through all three Dishevelled isoforms, as determined by epistasis experiments using the Dishevelled antagonist Dapper1 (DACT1). Suppression of either Dishevelled-1 or Dishevelled-3, but not Dishevelled-2, abolishes WNT3a activation of JNK. Activation of the small GTPases RhoA, Rac1 and Cdc42 operates downstream of Dishevelled, linking to the MEKK 1/MEKK 4-dependent cascade, and on to JNK activation. Chemical inhibitors of JNK (SP600125), but not p38 (SB203580), block WNT3a activation of JNK, whereas both the inhibitors attenuate the WNT3a–β-catenin pathway. These data reveal both common and unique signaling elements in WNT3a-sensitive pathways, highlighting crosstalk from WNT3a-JNK to WNT3a–β-catenin signaling.

Key words: WNT, β-catenin, JNK, Heterotrimeric G-proteins, Frizzled, G_o, Dishevelled, Planar cell polarity

This article has been cited by other articles:

				R. K. Bikkavilli, M. E. Feigin, and C. C. Malbon G{alpha}o mediates WNT-JNK signaling through Dishevelled 1 and 3, RhoA family members, and MEKK 1 and 4 in mammalian cells Development, February 1, 2008; 135(3): e1 - e1. [Full Text]