Research article summary (published 13 Feb 2006):

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

Full 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.

Author information

Author/s: Jarvis, Lesley A (LA); Toering, Stephanie J (SJ); Simon, Michael A (MA); Krasnow, Mark A (MA); Smith-Bolton, Rachel K (RK);

Affiliation: Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305-5307 USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Development (Cambridge, England) (Development), published in England. (Language: eng)

Reference: 2006-Mar; vol 133 (issue 6) : pp 1133-42

Dates: Created 2006/02/27; Completed 2006/05/22; Revised 2007/11/15;

PMID: 16481357, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Cell Line Drosophila Proteins - genetics; metabolism Drosophila melanogaster - genetics; growth & development; metabolism Gene Expression Regulation, Developmental Humans Intracellular Signaling Peptides and Proteins - genetics; metabolism Membrane Proteins - genetics; metabolism

Phosphotyrosine - metabolism Protein Binding Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatases - genetics; metabolism Protein Tyrosine Phosphatases, Non-Receptor Protein-Tyrosine Kinases - metabolism Signal Transduction Substrate Specificity

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Drosophila Proteins (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; sprouty protein, Drosophila (0) ; Phosphotyrosine (21820-51-9) ; Protein-Tyrosine Kinases (EC 2.7.1.112) ; PTPN11 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Protein Tyrosine Phosphatases (EC 3.1.3.48) ; Protein Tyrosine Phosphatases, Non-Receptor (EC 3.1.3.48) ; corkscrew protein, Drosophila (EC 3.1.3.48)

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