Activation of phosphoipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: Possible role in mitogenic signal transduction

Abstract

The effects of platelet-derived growth factor (PDGF) on phosphoiipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol’ indicating the activation of PLD acting on phosphatidylcholine (PG). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [ H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase G (PKG) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKG.