The sorbin homology domain: A motif for the targeting of proteins to lipidrafts

On phosphorylation of Cbl, the c-Cbl-associated protein (CAP)/Cbl complex d issociates from the insulin receptor and translocates to a lipid raft membr ane fraction to form a ternary complex with flotillin. Deletion analyses of the CAP gene identified a 115-aa region responsible for flotillin binding. This region is homologous to the peptide sorbin and is referred to as the sorbin homology (SoHo) domain. This domain is present in two other proteins , vinexin and ArgBP2. Vinexin also interacted with flotillin, and deletion of its SoHo domain similarly blocked flotillin binding. The overexpression of a CAP mutant in which the SoHo domain had been deleted (CAP SoHo) preven ted the translocation of Cbl to lipid rafts and subsequently blocked the re cruitment of CrkII and C3G. Moreover, overexpression of CAP Delta SoHo prev ented the stimulation of glucose transport and GLUT4 translocation by insul in. These results suggest a mechanism for Localization of signaling protein s to the lipid raft that mediates the compartmentalization of crucial signa l transduction pathways.