Editors' ChoiceAngiogenesis

Sprouty Blocks Branching

Science's STKE  13 Mar 2001:
Vol. 2001, Issue 73, pp. tw2
DOI: 10.1126/stke.2001.73.tw2

Sprouty (Spry) proteins inhibit fibroblast growth factor (FGF) and epidermal growth factor (EGF) signaling pathways in Drosophila, negatively affecting the developing trachea system. Lee et al. and Impagnatiello et al. both report that mammalian Spry proteins also antagonize growth factor signaling pathways that regulate branching of blood vessels in vertebrates. When overexpressed as a transgene in the endothelium and extraembryonic vasculature of mouse embryos, Spry caused poor branching of blood vessels and inhibited angiogenesis. Overexpression of Spry proteins in cultured endothelial cells inhibited differentiation into a netlike structure in response to growth factor treatment. Spry expression also blocked the proliferative effects of FGF, EGF, or vascular endothelial cell growth factor (VEGF), possibly because of increased expression of the cell-cycle inhibitor p21. Growth factor-induced cell migration was also inhibited by Spry. It is interesting that Spry proteins blocked activation of p42/44 MAP kinase in response to FGF or VEGF, but not EGF, indicating that Spry may not act only through the MAP kinase pathway. Impagnatiello et al. further show that mouse Spry proteins are palmitoylated, associated with caveolin, and are phosphorylated on serine in response to growth factor stimulation, but it remains unclear how these modifications regulate effects on growth factor signaling.

S. H. Lee, D. J. Schloss, L. Jarvis, M. A. Krasnow, J. L. Swain, Inhibition of angiogenesis by mouse Sprouty protein. J. Biol. Chem. 276, 4128-4133 (2001). [Abstract] [Full Text]

M.-A. Impagnatiello, S. Weitzer, G. Gannon, A. Compagni, M. Cotton, G. Christofori, Mammalian Sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J. Cell Biol. 152, 1087-1098 (2001). [Abstract] [Full Text]