SPRED proteins provide a NF-ty link to Ras suppression.
Mutations in the SPRED1 (Sprouty-related protein with an EVH [Ena/Vasp homology] domain 1) and NF1 (neurofibromatosis 1) genes underlie clinically related human disorders. The NF1-encoded protein neurofibromin is a Ras GTPase-activating protein (GAP) and can directly limit Ras activity. Spred proteins also negatively regulate Ras signaling, but the mechanism by which they do so is not clear. In the July 1, 2012, issue of Genes & Development, Stowe and colleagues (pp. 1421-1426) present evidence that Spred1 recruits neurofibromin to the membrane, where it dampens growth factor-induced Ras activity, providing a satisfying explanation for the overlapping features of two human diseases.
Massachusetts General Hospital Center for Cancer Research, Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129, USA. mcclatch@helix.mgh.harvard.edu
Andrea I
AI
McClatchey
Karen
K
Cichowski
D000818:Animals; D019080:Cafe-au-Lait Spots / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009456:Neurofibromatosis 1 / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D025542:Neurofibromin 1; D012097:Repressor Proteins