References
Query Results -- Details
MGI Accession ID: MGI:3613255
J Number: J:104986
Other Accession IDs:
Title: Neurofibromin binds to caveolin-1 and regulates ras, FAK, and Akt.
Authors: Boyanapalli M; Lahoud OB; Messiaen L; Kim B; Anderle de Sylor MS; Duckett SJ; Somara S; Mikol DD
Journal: Biochem Biophys Res Commun
Volume: 340
Issue: 4
Date: 2006 Feb 24
Year: 2006
Pages: 1200-8
Review Status: Peer Reviewed
Abstract:
Neurofibromin (Nf1) is an approximately 280 kDa protein having tumor suppressor function, presumably by virtue of its GTPase activating domain, but little is known regarding molecular aspects of its effector pathways. Caveolin-1 (Cav-1) regulates diverse signaling molecules and has itself been implicated as a tumor suppressor. Here we demonstrate that Nf1 binds to Cav-1's scaffolding domain and co-immunoprecipitates with Cav-1. Analysis of Nf1's primary structure reveals four potential caveolin binding domains, and interestingly, in individuals with neurofibromatosis I, missense mutations occur with high frequency in 3 of the 4 putative domains. We show that Nf1 modulates ras, Akt, and focal adhesion kinase pathways, thereby affecting cytoskeletal organization; moreover, Nf1's effects on signaling are altered when lipid rafts and caveolae are disrupted by cholesterol depletion. These novel findings provide insight into possible signaling mechanisms of Nf1 and suggest that together Nf1 and Cav-1 may coordinately regulate cell growth and differentiation.
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