CROSS-TALK OF MEMBRANE LIPID SIGNALING IN CELL DEATH AND SURVIVAL

点击翻译按钮获取中文摘要

We have previously proposed the notion that phospholipase D (PLD) plays an important role in the anti-apototic or survival signaling pathway. When PC12 cells were exposed to the oxidative stress (H_2O_2), the PLD activity was found to greatly increase at the early stage. It was demonstrated that the Pyk2 which acts as a scarffold and Src kinase are colsely associated with the H_2O_2-induced PLD activation. In addition, Pyk2 was found to be physically interacted with PLD as inferred by co-immunoprecipitation. Thus it was concluded that the Pyk2/Src/Akt pathway is of primary importance for the survival signaling at the early phase after the H_2O_2 stress.On the other hand, it has been known that sphingosine kinase produces sphingosine-1-phosphate whth exerts a survival signaling by its specific receptor activation (S1Ps). Furthermore, it was shown that the sphingosine kinase was much higher in the activity and protein expression level in camptothecin (CPT)-resistant PC3 cells as compared to CPT-sensitive LNCaP cells of human prostate cancer cells. Also, we have obtained the unexpected, interesting finding that CPT treatment enhanced the SPHK activity in a time-dependent manner, but the underlying mechanism remains to be defined. This can explain at least in part the CPT-resistance of PC3 cells.