Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells

Caveolae may function as microdomains for signaling that help to determine specific biological actions mediated by the insulin receptor (IR). Caveolin -1, a major component of caveolae, contains a scaffolding domain (SD) that binds to a caveolin-1 binding motif in the kinase domain of the in in vitro . To investigate the potential role of caveolin-1 in insulin signaling we o verexpressed wild-type (Cav-WT) or mutant (Cav-Mut; F92A/V94A in SD) caveol in-1 in either Cos-7 cells cotransfected with in or rat adipose cells (low and high levels of endogenous caveolin-1, respectively). Cav-WT coimmunopre cipitated with the in to a much greater extent than Cav-Mut, suggesting tha t the SD is important for interactions between caveolin-1 and the in in int act cells. We also constructed several in mutants with a disrupted caveolin -1 binding motif and found that these mutants were poorly expressed and did not undergo autophosphorylation. Interestingly, overexpression of Cav-WT i n Cos-7 cells significantly enhanced insulin-stimulated phosphorylation of Elk-l (a mitogen-activated protein kinase-dependent pathway) while overexpr ession of Cav-Mut was without effect. In contrast, in adipose cells, overex pression of either Cav-WT or Cav-Mut did not affect insulin-stimulated phos phorylation of a cotransfected ERK2 (but did significantly inhibit basal ph osphorylation of ERK2). Furthermore, we also observed a small inhibition of insulin-stimulated translocation of GLUT4 when either Cav-WT or Cav-Mut wa s overexpressed in adipose cells. Thus, interaction of caveolin-1 with ins may differentially modulate insulin signaling to enhance insulin action in Cos-7 cells but inhibit insulin's effects in adipose cells.