Sprouty Inhibits Raf

Science's STKE  05 Feb 2002:
Vol. 2002, Issue 118, pp. tw55-TW55
DOI: 10.1126/stke.2002.118.tw55

The first Sprouty protein was discovered in Drosophila as an inhibitor of fibroblast growth factor (FGF) signaling. Since then, four isoforms have been identified in mammals, and the Sprouty proteins are believed to inhibit the Ras-mitogen-activated protein kinase (MAPK) cascade. Yusoff et al. used transfected cells to show that human Sprouty 2 (hSpry2), and not mouse mSpry1 or mSpry4, inhibited FGF-mediated extracellular-signal-regulated kinase (ERK). Inhibition by hSpry2 was limited to the Ras-to-ERK pathway, because hSpry2 did not inhibit Jun-NH2-terminal kinase (JNK) or p38 activation. Using cells expressing constitutively activated mutants of Ras, the kinase Raf, or the kinase MEK (from the cascade Ras-Raf-MEK-ERK), Yusoff et al. positioned hSpry2 at the level of Raf. Raf activity from cells transfected with hSpry2 and stimulated with FGF was inhibited compared with that from cells not expressing hSpry2. Thus, at least the Spry2 isoform appears to be an inhibitor of the Ras-MAPK cascade at the level of Raf.

P. Yusoff, D.-H. Lao, S. H. Ong, E. S. M. Wong, J. Lim, T. L. Lo, H. F. Leong, C. W. Fong, G. R. Guy, Sprouty2 inhibits the Ras/MAP Kinase pathway by inhibiting the activation of Raf. J. Biol. Chem. 277, 3195-3201 (2002). [Abstract] [Full Text]