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http://purl.uniprot.org/citations/11457855http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11457855http://www.w3.org/2000/01/rdf-schema#comment"Caveolin-1 is the principal structural protein of caveolae membranes in fibroblasts and endothelia. Recently, we have shown that the human CAV-1 gene is localized to a suspected tumor suppressor locus, and mutations in Cav-1 have been implicated in human cancer. Here, we created a caveolin-1 null (CAV-1 -/-) mouse model, using standard homologous recombination techniques, to assess the role of caveolin-1 in caveolae biogenesis, endocytosis, cell proliferation, and endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, Cav-1 null mice are viable. We show that these mice lack caveolin-1 protein expression and plasmalemmal caveolae. In addition, analysis of cultured fibroblasts from Cav-1 null embryos reveals the following: (i) a loss of caveolin-2 protein expression; (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein isothiocyanate-albumin; and (iii) a hyperproliferative phenotype. Importantly, these phenotypic changes are reversed by recombinant expression of the caveolin-1 cDNA. Furthermore, examination of the lung parenchyma (an endothelial-rich tissue) shows hypercellularity with thickened alveolar septa and an increase in the number of vascular endothelial growth factor receptor (Flk-1)-positive endothelial cells. As predicted, endothelial cells from Cav-1 null mice lack caveolae membranes. Finally, we examined eNOS signaling by measuring the physiological response of aortic rings to various stimuli. Our results indicate that eNOS activity is up-regulated in Cav-1 null animals, and this activity can be blunted by using a specific NOS inhibitor, nitro-l-arginine methyl ester. These findings are in accordance with previous in vitro studies showing that caveolin-1 is an endogenous inhibitor of eNOS. Thus, caveolin-1 expression is required to stabilize the caveolin-2 protein product, to mediate the caveolar endocytosis of specific ligands, to negatively regulate the proliferation of certain cell types, and to provide tonic inhibition of eNOS activity in endothelial cells."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m105408200"xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Li M."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Zhang X.L."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Wang X.B."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Razani B."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Lisanti M.P."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Russell R.G."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Di Vizio D."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Marks C.B."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Pestell R.G."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Engelman J.A."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Schubert W."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Edelmann W."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Hou H. Jr."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Kneitz B."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Macaluso F."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Christ G.J."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/author"Lagaud G."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/date"2001"xsd:gYear
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/pages"38121-38138"xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/title"Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities."xsd:string
http://purl.uniprot.org/citations/11457855http://purl.uniprot.org/core/volume"276"xsd:string
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