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.