Sprouty (Spry) proteins restrict branching of the developing trachael systems in Drosophila and mouse, likely through inhibition of fibroblast growth factor (FGF) signaling. Both Lee et al. and Impagnatiello et al. report that mammalian Spry proteins antagonize growth factor signaling pathways that regulate the branching of blood vessels in vertebrates. When overexpressed in the endothelium and extra-embryonic vasculature of mouse embryos, Spry caused poor branching of blood vessels and inhibited angiogenesis; overexpression of Spry proteins in cultured endothelial cells blocked growth factor-induced differentiation into a netlike structure. Spry expression also blocked the proliferative effects of FGF, epidermal growth factor (EGF), and vascular endothelial cell growth factor (VEGF), possibly because of increased expression of the cell-cycle inhibitor p21. Impagnatiello et al. also show that mouse Spry proteins are palmitoylated and associated with caveolin, although not in lipid rafts. Thus, this family of membrane-bound proteins appears to influence morphogenesis through regulation of several receptor tyrosine kinase pathways. — LDC
J. Biol. Chem.276, 4128 (2001); J. Cell Biol.152, 1087 (2001).