Differing signal transductions elicited by three isoforms of platelet-derived growth factor in vascular smooth muscle cells.
The differing signal transductions elicited by three isoforms of platelet-derived growth factor (PDGF) were studied in cultured rat vascular smooth muscle cells (VSMC), which show different mitogenic responses to the three PDGF isoforms. PDGF-BB elicited a variety of cellular signals, including the phosphorylation on tyrosine of phospholipase C-gamma 1 (PLC-gamma 1) and the PDGF receptor, formation of inositol 1,4,5-trisphosphate and diacylglycerol, degradation of phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) and elevation of intracellular calcium ([Ca2+]i). However, PDGF-AB failed to show some of these signals, although it stimulated [3H]thymidine incorporation to almost the same extent as PDGF-BB. Importantly, phosphorylation on tyrosine of the PLC-gamma 1 was far less (< 6.25%) in the case of PDGF-AB than that of PDGF-BB when assessed by immunoblotting. On the other hand, calcium ion entry from the extracellular medium was comparable in PDGF-AB- and PDGF-BB- stimulated VSMC. PDGF-AA, which did not stimulate [3H]thymidine incorporation, failed to show any of these effects with the exception of diacylglycerol formation. These observations suggest that the three PDGF isoforms stimulate different signal transduction pathways and that calcium ion entry, but not tyrosine phosphorylation of PLC-gamma 1, is essential for PDGF-induced mitogenesis in VSMC.
Kondo
T
T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Konishi
F
F
Inui
H
H
Inagami
T
T
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium; D013936:Thymidine