Receptors for platelet-derived growth factor on microvascular endothelial cells.
Endothelial cells are widely thought to be unresponsive to platelet-derived growth factor (PDGF) and devoid of PDGF receptors. However, in examining the growth factor responses of microvascular endothelial cells isolated from human omental adipose tissue, we detected PDGF-induced tyrosine phosphorylation of an 180-kD glycoprotein, subsequently identified as the cellular receptor for PDGF by specific immunoprecipitation. Scatchard analysis of 125I-PDGF binding to human microvascular endothelial cells revealed 30,000 PDGF receptors/cell with a kD of 0.14 nM. PDGF stimulated tyrosine phosphorylation of PDGF and other cellular proteins in a dose- and time-dependent manner, with half-maximal receptor phosphorylation occurring at 0.3 nM recombinant human PDGF-BB within 1 min of PDGF exposure. Normal cellular consequences of receptor activation were also observed, including tyrosine phosphorylation of a 42-kD protein and serine phosphorylation of ribosomal protein S6. Furthermore, PDGF was mitogenic for these cells. The finding of functional PDGF receptors on human microvascular endothelial cells suggests an important direct role for PDGF in neovascularization.
Beitz
J G
JG
Roger Williams Cancer Center, Providence, RI.
Kim
I S
IS
Calabresi
P
P
Frackelton
A R
AR
D000273:Adipose Tissue / Q000098:blood supply; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008833:Microcirculation; D009852:Omentum; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor
D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor