Platelet-derived growth factor activates phospholipase D and chemotactic responses in vascular smooth muscle cells.
Platelet-derived growth factor (BB dimer; PDGF-BB) stimulates a mitogenic response in A-10 vascular smooth muscle cells. In addition, PDGF-BB stimulates phospholipase D activity against phosphatidylcholine in A-10 cells. This response was observed as a rapid metabolism of phosphatidylcholine to phosphatidate and choline; a subsequent metabolism generates sustained levels of diacylglycerol. The accumulation of phosphatidylethanol, a transphosphatidylation product of phospholipase D, was obvious in PDGF-treated cells. PDGF-BB also stimulates a chemotactic response in A-10 cells. The concentrations of PDGF-BB required to stimulate mitogenesis, phospholipase D activity and chemotaxis are similar. This finding shows that PDGF induces a variety of cellular responses and suggests that these responses may share common metabolic pathways. That conception was tested by investigating the activity of the different PDGF dimers. PDGF-AA had little or no activity in A-10 cells for any of the responses measured. PDGF-AB and PDGF-BB were equally potent in stimulating mitogenic responses. However, the AB heterodimer was only half as active as PDGF-BB with respect to activation of phospholipase D and chemotactic responses. These results demonstrate that PDGF stimulates phospholipase D in vascular smooth muscle cells. In addition, the data indicate that different PDGF dimers can transduce varying signals and suggest a link between the mechanisms by which PDGF-BB activates phospholipase D and the chemotactic response.
Welsh
C J
CJ
W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
Schmeichel
K
K
McBride
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020404:Glycerophospholipids; D007700:Kinetics; D046911:Macromolecular Substances; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats
D004075:Diglycerides; D020404:Glycerophospholipids; D046911:Macromolecular Substances; D010712:Phosphatidic Acids; D010743:Phospholipids; D010982:Platelet-Derived Growth Factor; C051521:phosphatidylethanol; D010739:Phospholipase D; D002794:Choline