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

• Lesley A. Jarvis

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

• Stephanie J. Toering

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

• Michael A. Simon

  Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020 USA.

• Mark A. Krasnow

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

• Rachel K. Smith-Bolton

  Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020 USA.

抄録

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 Drosophilaand 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.

収録刊行物

• Development

  Development 133 (6), 1133-1142, 2006-03-15

  The Company of Biologists

キーワード

• Developmental Biology
• Molecular Biology

詳細情報

• CRID: 1360576120772849024
• NII論文ID: 30002334016
• DOI: 10.1242/dev.02255
• ISSN: 14779129
• ISSN: 09501991
• Web Site: http://journals.biologists.com/dev/article-pdf/133/6/1133/1518407/1133.pdf
• データソース種別:
  • Crossref
  • CiNii Articles