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

First published online 15 February 2006
doi: 10.1242/dev.02255

This Article Figures Only Full Text Full Text (PDF) OA All Versions of this Article: dev.02255v1 dev.02255v2 133/6/1133    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 Jarvis, L. A. Articles by Smith-Bolton, R. K. Search for Related Content PubMed PubMed Citation Articles by Jarvis, L. A. Articles by Smith-Bolton, R. K.

Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases

Lesley A. Jarvis^1,*,, Stephanie J. Toering^1,*,, Michael A. Simon², Mark A. Krasnow^1,¶ and Rachel K. Smith-Bolton^2,*,

¹ Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5307 USA.
² Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020 USA.

^¶ Author for correspondence (e-mail: krasnow{at}cmgm.stanford.edu)

Accepted 16 December 2005

Drosophila Corkscrew protein and its vertebrate ortholog SHP-2 (now known as Ptpn11) positively modulate receptor tyrosine kinase (RTK) signaling during development, but how these tyrosine phosphatases promote tyrosine kinase signaling is not well understood. Sprouty proteins are tyrosine-phosphorylated RTK feedback inhibitors, but their regulation and mechanism of action are also poorly understood. Here, we show that Corkscrew/SHP-2 proteins control Sprouty phosphorylation and function. Genetic experiments demonstrate that Corkscrew/SHP-2 and Sprouty proteins have opposite effects on RTK-mediated developmental events in Drosophila and an RTK signaling process in cultured mammalian cells, and the genes display dose-sensitive genetic interactions. In cultured cells, inactivation of SHP-2 increases phosphorylation on the critical tyrosine of Sprouty 1. SHP-2 associates in a complex with Sprouty 1 in cultured cells and in vitro, and a purified SHP-2 protein dephosphorylates the critical tyrosine of Sprouty 1. Substrate-trapping forms of Corkscrew bind Sprouty in cultured Drosophila cells and the developing eye. These results identify Sprouty proteins as in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases and show how Corkscrew/SHP-2 proteins can promote RTK signaling by inactivating a feedback inhibitor. We propose that this double-negative feedback circuit shapes the output profile of RTK signaling events.

Key words: Sprouty (Spry), Corkscrew (Csw), Ptpn11 (SHP-2), Tyrosine phosphatase, Receptor tyrosine kinase (RTK) signaling, Drosophila

This article has been cited by other articles:

				A. Horowitz and M. Simons Branching Morphogenesis Circ. Res., October 10, 2008; 103(8): 784 - 795. [Abstract] [Full Text] [PDF]

				Y. G. Langdon, S. C. Goetz, A. E. Berg, J. T. Swanik, and F. L. Conlon SHP-2 is required for the maintenance of cardiac progenitors Development, November 15, 2007; 134(22): 4119 - 4130. [Abstract] [Full Text] [PDF]

				K. Bundschu, U. Walter, and K. Schuh The VASP-Spred-Sprouty Domain Puzzle J. Biol. Chem., December 1, 2006; 281(48): 36477 - 36481. [Abstract] [Full Text] [PDF]