PV-1 is negatively regulated by VEGF in the lung of caveolin-1, but not caveolin-2, null mice.
An N-glycosylated 60-kDa PV-1 protein that binds heparin was detected in mouse lung from a single mRNA transcript. In the absence of disulfide bond reduction PV-1 is detected as a dimer or large molecular weight oligomer. In the lung of Cav-1, but not Cav-2, null mice the amount of PV-1 protein is diminished, with no detectable change in mRNA level. PV-1 does not fractionate with caveolae on a sucrose density gradient, but the Cav-1 protein is detected in fractions following immunoprecipitation with PV-1 antibodies. Both PV-1 and Cav-1 localize to alveolar endothelial cells, but PV-1 is concentrated at the abluminal and Cav-1 at the luminal cell surface with minimal colocalization. In the Cav-1 null lungs, PV-1 is nearly undetectable in endothelial cells, but remains unchanged in pneumocytes and bronchial epithelial cells. Injection of a VEGF-R2 inhibitor increased PV-1 protein in lung of Cav-1 null, but not Cav-2 or wild-type mice. These data indicate that the PV-1 protein is negatively regulated in pulmonary endothelial cells by VEGF-R2 signaling.
Hnasko
Robert
R
United States Department of Agriculture, Agricultural Research Service, Pacific West Area, Western Regional Research Center, Foodborne Contaminants Research Unit, Albany, California, USA.
Frank
Philippe G
PG
Ben-Jonathan
Nira
N
Lisanti
Michael P
MP
D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000737:chemistry; D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics*; D051243:Caveolin 2 / Q000235:genetics*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006493:Heparin; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002352:Carrier Proteins; C495541:Cav1 protein, mouse; C495545:Cav2 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D008565:Membrane Proteins; C486772:Plvap protein, mouse; D012333:RNA, Messenger; D006493:Heparin; D040301:Vascular Endothelial Growth Factor Receptor-2