PDGF-induced activation of phospholipase C is not required for induction of DNA synthesis .

Hill TD ; Dean NM ; Mordan LJ ; Lau AF ; Kanemitsu MY ; Boynton AL

Cancer Research Center of Hawaii , University of Hawaii , Honolulu 96813 .

Science 248 : 1660-3 ( 1990)

Abstract
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 .