Studies on the coupling mechanism of phosphatidyl-choline turnover and protein kinase C activation.

点击翻译按钮获取中文摘要

The hydrolysis of phosphatidylcholine by phospholipase D (PLD) is caused by a wide variety of external signngals, and is now thought to generate several lipid messengers or mediators such as diacylglycerol which is essential to protein kinase C (PKC) activation. To date, some of small molecular weight G-proteins and protein phosphorylation may be involved in the activation of PLD,although precise mechanism of the enzyme regulation remains to be elucidated. In the series of the present research, we have found that phorbolester or diacylglycerol enhanced GTPRgammaS-dependent PLD activity in an ATP-Mg^<2+> -dependent manner in streptolysin-O-permeabilized HL-60 cells. This enhancement was totally inhibited not only by PKC inhibitors but by tyrosine kinase inhibitors suggesting the involvement of protein kinase C and tyrosine kinase.In a cell-free system, GTPgammaS was essential to PLD activity using spleen lysates. We also found that a novel protein factor other than G-protein is necessary for the action of small molecular weight G-proteins (ADP ribosylation factor or Rho). Purification and characterization of this novel protein is under investigation.