Sprouty Proteins, A New Family of Receptor Tyrosine Kinase Inhibitors

In Drosophila, Sprouty was originally identified as an antagonist of tracheal branching and shown to be a general inhibitor of receptor tyrosine kinase. Recently, four mammalian homologues have been isolated. All Sprouty proteins exhibit a unique, highly conserved, cysteinerich C-terminal domain. Genetic and biochemical data indicate that Sprouty proteins antagonize receptor tyrosine kinase signaling through specific inhibition of the Ras / Raf / MAP Kinase pathway by preventing Ras activation. Expression of sprouty genes is regulated by FGF in a negative autoregulatory loop and is localized to known domains of FGF signaling in the developing embryo. Overexpression studies suggest that vertebrate sprouty genes may be important regulators of several developmental processes. In particular, sprouty may play a role during the branching morphogenesis involved in angiogenesis, or the formation of the lung and the kidney, but also during gastrulation or limb formation.