Members of the Sprouty family (Sprouty 1-4) are inducible negative regulators of growth factors that act through tyrosine kinase receptors. Mammalian Sprouty homologs share a well-conserved cysteine-rich carboxy-terminal domain with their Drosophila counterparts. Sprouty proteins are cytoplasmic in unstimulated cells, but in cells stimulated by growth factors they anchor to the plasma membrane by palmitoylation. Sprouty 1 and 2 associate with caveolin-1 in perinuclear and vesicular structures and are phosphorylated on serine residues. Sprouty 2 can associate with c-Cbl, a downregulator of RTK signaling, and inhibit the activities of several growth factors. Unlike the widely expressed Sprouty members 1, 2 and 4, Sprouty 3 expression is restricted to adult brain and testis. Sprouty 4 is a target of the WNT/b-catenin signaling pathway in progenitor cells. In conclusion, members of Sprouty inhibit FGF and VEGF-mediated cell proliferation, suggesting that they may regulate angiogenesis in normal and disease processes.
