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

First published online 10 July 2006
doi: 10.1242/dev.02467

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02467v1 133/16/3063    most recent 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 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 Murray, M. J. Articles by Brand, A. H. Search for Related Content PubMed PubMed Citation Articles by Murray, M. J. Articles by Brand, A. H.

The Fes/Fer non-receptor tyrosine kinase cooperates with Src42A to regulate dorsal closure in Drosophila

¹ The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
² Centre for the Molecular Genetics of Development, Research School of Biological Sciences, Australian National University, Canberra ACT 0200, Australia.

^* Author for correspondence (e-mail: ahb{at}mole.bio.cam.ac.uk)

Accepted 30 May 2006

Fes/Fer non-receptor tyrosine kinases regulate cell adhesion and cytoskeletal reorganisation through the modification of adherens junctions. Unregulated Fes/Fer kinase activity has been shown to lead to tumours in vivo. Here, we show that Drosophila Fer localises to adherens junctions in the dorsal epidermis and regulates a major morphological event, dorsal closure. Mutations in Src42A cause defects in dorsal closure similar to those seen in dfer mutant embryos. Furthermore, Src42A mutations enhance the dfer mutant phenotype, suggesting that Src42A and DFer act in the same cellular process. We show that DFer is required for the formation of the actin cable in leading edge cells and for normal rates of dorsal closure. We have isolated a gain-of-function mutation in dfer (dfer^gof) that expresses an N-terminally fused form of the protein, similar to oncogenic forms of vertebrate Fer. dfer^gof blocks dorsal closure and causes axon misrouting. We find that in dfer loss-of-function mutants ß-catenin is hypophosphorylated, whereas in dfer^gof ß-catenin is hyperphosphorylated. Phosphorylated ß-catenin is removed from adherens junctions and degraded, thus implicating DFer in the regulation of adherens junctions.

Key words: Drosophila, Fes, Fer, Tyrosine kinase, Src, Adherens junction, Dorsal closure, ß-catenin

This article has been cited by other articles:

				C. Bakal, R. Linding, F. Llense, E. Heffern, E. Martin-Blanco, T. Pawson, and N. Perrimon Phosphorylation Networks Regulating JNK Activity in Diverse Genetic Backgrounds Science, October 17, 2008; 322(5900): 453 - 456. [Abstract] [Full Text] [PDF]

				N. Gorfinkiel and A. M. Arias Requirements for adherens junction components in the interaction between epithelial tissues during dorsal closure in Drosophila J. Cell Sci., September 15, 2007; 120(18): 3289 - 3298. [Abstract] [Full Text] [PDF]

				W. Sangrar, Y. Gao, M. Scott, P. Truesdell, and P. A. Greer Fer-Mediated Cortactin Phosphorylation Is Associated with Efficient Fibroblast Migration and Is Dependent on Reactive Oxygen Species Generation during Integrin-Mediated Cell Adhesion Mol. Cell. Biol., September 1, 2007; 27(17): 6140 - 6152. [Abstract] [Full Text] [PDF]