Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases
Open Access
- 15 March 2006
- journal article
- Published by The Company of Biologists in Development
- Vol. 133 (6), 1133-1142
- https://doi.org/10.1242/dev.02255
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.Keywords
This publication has 46 references indexed in Scilit:
- Tyrosine Phosphorylation of Sprouty Proteins Regulates Their Ability to Inhibit Growth Factor Signaling: A Dual Feedback LoopMolecular Biology of the Cell, 2004
- Shp2, an SH2-containing Protein-tyrosine Phosphatase, Positively Regulates Receptor Tyrosine Kinase Signaling by Dephosphorylating and Inactivating the Inhibitor SproutyPublished by Elsevier BV ,2004
- Molecular Mechanism for a Role of SHP2 in Epidermal Growth Factor Receptor SignalingMolecular and Cellular Biology, 2003
- Calcium oscillations in T-cells: mechanisms and consequences for gene expressionBiochemical Society Transactions, 2003
- Spectrum of mutations in PTPN11 and genotype–phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndromeEuropean Journal of Human Genetics, 2003
- SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF β-receptorOncogene, 2002
- The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functionsCell Research, 2000
- SHP-2, SH2-containing protein tyrosine phosphatase-2The International Journal of Biochemistry & Cell Biology, 1998
- Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activationCell, 1995
- Neuronal differentiation in the Drosophila ommatidiumDevelopmental Biology, 1987