Expression of transforming growth factor type III receptor in vascular endothelial cells increases their responsiveness to transforming growth factor beta 2.
Bovine aortic endothelial cells (BAECs) express both type I and type II receptors for transforming growth factor beta (TGF beta). These cells respond to TGF beta 1 but are relatively refractory to another isoform of TGF beta, termed TGF beta 2. TGF beta s are thought to signal through receptor complexes composed of type I and/or type II receptors, both of which appear to be functional serine-threonine kinases. The TGF beta type III receptor, on the other hand, does not seem to have any direct signaling capacity. We have now stably transfected BAECs with the type III receptor cDNA. These cells displayed surface expression of the type III receptor protein, as determined by cross-linking with iodinated TGF beta 1 and immunoprecipitation with antibodies to the type III receptor protein. Transfected BAECs exhibit increased responsiveness to TGF beta 2 by several different criteria including an increase in plasminogen activator inhibitor-1 protein and inhibition of migration and proliferation. Thus, the type III receptor protein may play a role in presenting TGF beta 2 to the type II receptor and increase responsiveness to TGF beta 2 to a level comparable to that of TGF beta 1.
Sankar
S
S
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Mahooti-Brooks
N
N
Centrella
M
M
McCarthy
T L
TL
Madri
J A
JA
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011485:Protein Binding; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
D017395:Plasminogen Activator Inhibitor 1; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan