Scaffold Proteins

Endocytosis Intersectin with Ras

Science's STKE  21 Mar 2000:
Vol. 2000, Issue 24, pp. tw2
DOI: 10.1126/stke.2000.24.tw2

Intersectin is a scaffolding protein involved in clathrin-mediated endocytosis that interacts through at least 3 domains with several proteins. One of the domains is a group of 5 COOH-terminal SH3 domains. The SH3 domains mediate binding of intersectin with synaptojanin and dynamin, enzymes that participate in the formation of clathrin-coated vesicles. Tong et al. identified mSos1, the Ras guanine nucleotide exchange factor, as another binding partner for the first SH3 domain of intersectin, SH3A. Intersectin and mSos1 coimmunoprecipitate from brain extracts and are found in a large protein complex that excludes Grb2 in sucrose density gradients. The SH3A domain of intersectin competes with Grb2 for binding to mSos1, and overexpression of the SH3 domains of intersectin attenuates Ras activation. The authors have identified another link between endocytic and signal transduction machineries.

Tong, X.-K., Hussain, N.K., de Heuvel, E., Kurakin, A., Abi-Jaoude, E., Quinn, C.C., Olson, M.F., Marais, R., Baranes, D., Kay, B.K., and McPherson, P.S. (2000) The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain. EMBO J. 19: 1263-1271. [Abstract] [Full Text]