Transduction of mitogenic activity of platelet-derived growth factor (PDGF) AB by PDGF-beta receptor without participation of PDGF-alpha receptor in vascular smooth muscle cells.
In cultured rat vascular smooth muscle cells, platelet-derived growth factor (PDGF) beta receptor was expressed at a high level, whereas PDGF-alpha receptor was not detected. PDGF-BB showed a high binding activity at 4 degrees C in the cells and was not displaced by PDGF-AA or -AB. This result indicates that PDGF-AB as well as PDGF-AA does not bind to the cells lacking PDGF-alpha receptor at 4 degrees C. However, at 37 degrees C, PDGF-AB bound to the cells and induced the internalization of PDGF-beta receptor. DNA synthesis was also stimulated potentially by PDGF-AB as well as PDGF-BB in the cells, although PDGF-AA was completely inactive. At 37 degrees C, PDGF-AB caused tyrosine phosphorylation of a group of proteins including PDGF-beta receptor and phospholipase C-gamma 1, but at a slower rate than PDGF-BB. At 4 degrees C, PDGF-AB did not stimulate protein tyrosine phosphorylation, whereas PDGF-BB did. A chemical cross-linking experiment showed that PDGF-beta receptor was dimerized by PDGF-AB as well as PDGF-BB. These results indicate that PDGF-beta receptor binds PDGF-AB without participation of PDGF-alpha receptor at 37 degrees C (but not at 4 degrees C), and PDGF-AB as well as PDGF-BB acts as a potent mitogen in the vascular smooth muscle cells.
Inui
H
H
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Kitami
Y
Y
Kondo
T
T
Inagami
T
T
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor