PDGF-induced activation of phospholipase C is not required for induction of DNA synthesis.
Platelet-derived growth factor (PDGF) induction of DNA synthesis is believed to involve activation of phospholipase C (PLC) and subsequent accumulation of inositol 1,4,5-triphosphate [I(1,4,5)P3], increase in intracellular Ca2+, activation of protein kinase C (PKC), and receptor down regulation. Generation of these events is triggered by the tyrosine protein kinase (TPK) activity of the PDGF receptor. The TPK inhibitor genistein blocked PDGF induction of these events, including DNA synthesis, with the exception of receptor down regulation. PDGF-induced phosphotyrosine phosphorylations, including receptor autophosphorylation, were inhibited by genistein. Removal of genistein and PDGF resulted in DNA synthesis without the occurrence of PLC activation. These findings indicate that these early events, with the exception of receptor down regulation, are not necessary for PDGF-induced DNA synthesis.
Hill
T D
TD
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Dean
N M
NM
Mordan
L J
LJ
Lau
A F
AF
Kanemitsu
M Y
MY
Boynton
A L
AL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004789:Enzyme Activation; D019833:Genistein; D007295:Inositol Phosphates / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D002712:Chlorides; D007295:Inositol Phosphates; D007529:Isoflavones; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D008094:Lithium; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D018021:Lithium Chloride; D002118:Calcium; D004121:Dimethyl Sulfoxide