Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II

► Caveolin-1 gene transfer interferes with the angiotensin II-induced EGF receptor transactivation cascade including ADAM17 activation. ► Caveolin-1 gene transfer inhibited angiotensin II-induced hypertrophy and migration of vascular smooth muscle cells. ► ADAM17 colocalizes with Cav1 in the lipid raft fractions. ► A disruption of the lipid raft structure leads to HB-EGF shedding and EGF receptor transactivation.