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

First published online 19 September 2007
doi: 10.1242/dev.011577

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.011577v1 134/20/3677    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed 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 Ruel, L. Articles by Thérond, P. P. Search for Related Content PubMed PubMed Citation Articles by Ruel, L. Articles by Thérond, P. P. Social Bookmarking                         What's this?

Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling

Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 02, France.

^* Author for correspondence (e-mail: therond{at}unice.fr)

Accepted 24 July 2007

The Hedgehog (Hh) family of secreted proteins is involved both in developmental and tumorigenic processes. Although many members of this important pathway are known, the mechanism of Hh signal transduction is still poorly understood. In this study, we analyse the regulation of the kinesin-like protein Costal2 (Cos2) by Hh. We show that a residue on Cos2, serine 572 (Ser572), is necessary for normal transduction of the Hh signal from the transmembrane protein Smoothened (Smo) to the transcriptional mediator Cubitus interruptus (Ci). This residue is located in the serine/threonine kinase Fused (Fu)-binding domain and is phosphorylated as a consequence of Fu activation. Although Ser572 does not overlap with known Smo- or Ci-binding domains, the expression of a Cos2 variant mimicking constitutive phosphorylation and the use of a specific antibody to phosphorylated Ser572 showed a reduction in the association of phosphorylated Cos2 with Smo and Ci, both in vitro and in vivo. Moreover, Cos2 proteins with an Ala or Asp substitution of Ser572 were impaired in their regulation of Ci activity. We propose that, after activation of Smo, the Fu kinase induces a conformational change in Cos2 that allows the disassembly of the Smo-Fu-Cos2-Ci complex and consequent activation of Hh target genes. This study provides new insight into the mechanistic regulation of the protein complex that mediates Hh signalling and a unique antibody tool for directly monitoring Hh receptor activity in all activated cells.

Key words: Costal2, Development, Drosophila, Hedgehog, Phosphorylation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

Hh signals break up

Development 2007 134: e2003. [Full Text]  

This article has been cited by other articles:

				L. Ruel, A. Gallet, S. Raisin, A. Truchi, L. Staccini-Lavenant, A. Cervantes, and P. P. Therond Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signaling J. Cell Sci., October 15, 2007; 120(20): e2007 - e2007. [Full Text]