The fully linked HTML version of this article has now been published.
Development ePress online publication date 15 Feb 2006
doi: 10.1242/dev.02255
Research article
(2006)Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases
Lesley A. Jarvis,
Stephanie J. Toering,
Michael A. Simon,
Mark A. Krasnow*,
and
Rachel K. Smith-Bolton
* Author for correspondence (e-mail: krasnow{at}cmgm.stanford.edu)
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.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G R Guy, R A Jackson, P Yusoff, and S Y Chow
Sprouty proteins: modified modulators, matchmakers or missing links?
J. Endocrinol.,
November 1, 2009;
203(2):
191 - 202.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Edwin, K. Anderson, C. Ying, and T. B. Patel
Intermolecular Interactions of Sprouty Proteins and Their Implications in Development and Disease
Mol. Pharmacol.,
October 1, 2009;
76(4):
679 - 691.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. S. Zhang, E. Hao, J. Yu, W. Liu, J. Wang, F. Levine, and G.-S. Feng
Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic {beta}-cells
PNAS,
May 5, 2009;
106(18):
7531 - 7536.
[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]
|
 |
|
© The Company of Biologists Ltd 2006