Functional cooperationbetween integrins andgrowth factor receptors has been reported for several systems, oneofwhich is the modulation of insulin signaling by avb3 integrin. Plasminogen activator inhibitor type-1 (PAI-1), competes withavb3 integrin for vitronectin (VN) binding. Here we report that PAI-1, in a VN-dependent manner, prevents the cooperation of avb3 integrin with insulin signaling in NIH3T3 fibroblasts, resulting in a decrease in insulin-induced protein kinase B (PKB) phosphorylation, vascular endothelial growth factor (VEGF) expression and cell migration. .