Reference Report

Reference
Citation	Jarvis, L.A., Toering, S.J., Simon, M.A., Krasnow, M.A., Smith-Bolton, R.K. (2006). Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development 133(6): 1133--1142. (Export to RIS)
FlyBase ID	FBrf0190302
Publication Type	Research paper
PubMed ID	16481357
PubMed Abstract	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.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (17)
	Avic\GFP^Scer\UAS.cUa bnl^unspecified btl^T:Zzzz\FLAG csw::Src64B^{C583S.hs.2sev} csw::Src64B^hs.2sev csw::Src64B^{src90.Scer\UAS} csw^CS.Act5C csw^CS.hs.2sev csw^Esev1A-eOP csw^{G547E.hs.2sev} csw^hs.2sev Scer\GAL4^btl.PS Scer\GAL4^hs.2sev sty^Scer\UAS.cHa sty^{Y201F.Scer\UAS} sty^Δ5 w^+mC
Constructs (10)
	P{GAL4-btl.S} P{GAL4-Hsp70.sev} P{SE-csw^C583Ssrc90} P{sevhs-csw^CS} P{sevhs-csw^G547E} P{sevhs-csw^src90} P{UAS-csw.src90} P{UAS-GFP.U} P{UAS-spry.Y201F} P{UAS-sty.H}
Genes (9)
	Avic\GFP bnl btl csw csw::Src64B Scer\GAL4 sty T:Zzzz\FLAG w
Insertions (3)
	P{UAS-spry.Y201F}13 P{UAS-spry.Y201F}15 P{UAS-spry.Y201F}37
Natural transposons (1)
	P-element