Caveolin-1 (Cav-1) regulates both insulin like growth factor receptor (IGF-IR) and integrin beta 1 function. However, the role of Cav-1 in IGF-IR/integrin beta 1 cross talk remains to be established. In this Study, we observed that IGF-I did not induce integrin beta 1 internalization but its plasma membrane reorganization. In particular, we found a rapid and transient association between integrin beta 1 and Cav-1 followed by the enrichment of integrin beta 1 in lipid rafts. To determine the role of Cav-1 in this process, we transfected Hacat cells with small interfering RNA specific for Cav-1 (siRNA-Cav-1) and with a scrambled siRNA as control (siRNA-Ctr). Cav-1 down regulated Hacat cells were then Stimulated with IGF-I and analyzed by immunofluorescence and flow cytometry. We found that Cav-1 silencing abolished the recruitment of integrin beta 1 to lipid rafts in the presence of IGF-I. These data demonstrate that IGF-IR/integrin beta 1 cross talk is followed by integrin beta 1 lipid raft compartmentalization and that Cav-1 is required for this process. (C) 2009 Elsevier Inc. All rights reserved.