title: Caveolin-1 detergent solubility and association with endothelial nitric oxide synthase is modulated by tyrosine phosphorylation.
abstract: Caveolin-1 and endothelial nitric oxide synthase (eNOS) are associated within endothelial caveolae. We have shown previously that eNOS is translocated to the detergent-insoluble, cytoskeletal fraction of bovine aortic endothelial cells (BAEC) in response to bradykinin (BK)-stimulation or tyrosine phosphatase inhibition. In the present study, we have examined whether caveolin-1 is similarly translocated in response to these or other stimuli. Exposure of BAEC to the eNOS-activating agonists, BK, histamine, or ATP produces transient increases in the amounts of detergent-insoluble caveolin-1. Increases in insolubility are blocked by tyrosine kinase inhibitors and are potently mimicked by tyrosine phosphatase inhibitors. Increased insolubility is accompanied by an increased association of caveolin-1 with eNOS and inhibition of eNOS catalytic activity. Agonist-activation of eNOS in endothelial cells thus appears to involve tyrosine phosphorylation-dependent changes in the interaction of eNOS with caveolin-1. Increased interaction of eNOS with caveolin-1 may deactivate the enzyme subsequent to its activation by Ca2+/calmodulin.
authors.affiliation: Vascular Biology Center, Department of Pediatrics, Medical College of Georgia, Augusta 30912, USA.
authors.forename: V J
authors.initials: VJ
authors.lastname: Venema
authors.forename: R
authors.initials: R
authors.lastname: Zou
authors.forename: H
authors.initials: H
authors.lastname: Ju
authors.forename: M B
authors.initials: MB
authors.lastname: Marrero
authors.forename: R C
authors.initials: RC
authors.lastname: Venema
mesh_terms: D000818:Animals; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D014443:Tyrosine; D019001:Nitric Oxide Synthase