Participation of diacylglycerol kinase in mitogenic signal transduction induced by platelet-derived growth factor in vascular smooth muscle cells.
In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF), stimulated phosphatidic acid synthesis by activating both of the two alternative pathways, diacyglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was partially inhibited by genistein or R 59022, but these inhibitors had no effect on phorbol ester-induced DNA synthesis. Further, the specific effects of these inhibitors on PDGF-induced DNA synthesis were additive.
Inui
H
H
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Kondo
T
T
Konishi
F
F
Kitami
Y
Y
Inagami
T
T
D000470:Alkaloids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D019852:Diacylglycerol Kinase; D004789:Enzyme Activation; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine; D013844:Thiazoles / Q000494:pharmacology
D000470:Alkaloids; D007529:Isoflavones; D008934:Mitogens; D009227:Myristic Acids; D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011744:Pyrimidinones; D011994:Recombinant Proteins; D013844:Thiazoles; D019814:Myristic Acid; D000077214:Becaplermin; D016718:Arachidonic Acid; D004247:DNA; C047505:R 59022; D019833:Genistein; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine