Phospholipase C : Diversity of isoenzyme functions and signal transduction.

磷脂酶C（PLC）同功酶家族通过G蛋白介导的途径的激活已被广泛表明在许多不同的细胞和组织中。尽管G蛋白依赖性刺激PLC的证据是丰富的，但关于通过G蛋白介导的途径抑制PLC的报道最近才开始出现。此外，已经证明凝溶胶蛋白（肌动蛋白调节蛋白）具有磷脂酰肌醇（PtdIns）结合区域，并且必须被Ca^2+激活。虽然凝溶胶蛋白是普遍存在于正常哺乳动物组织中，相对知之甚少的神经PtdIns-PLC系统中的作用。本研究表明：（1）大鼠大脑皮层膜保留了G蛋白非依赖性的PLC活性抑制作用;（2）小鼠神经母细胞瘤TBJ细胞中，过表达凝溶胶蛋白对表皮生长因子（EGF）受体的激活作用有影响，EGF受体介导了IP_3的产生。两种多样的功能a ...更多信息 结果表明：（1）脑皮层膜上的鸟嘌呤核苷酸对PLC活性有抑制作用，提示鸟嘌呤核苷酸对PLC系统可能有双重作用。大脑皮质膜表达较多的PLC-β 1同工酶。由于PLC-β_1是G蛋白介导的信号通路的效应子，我们的研究表明不同的G蛋白通过一个共同的机制调节PLC的活性，该机制尚待确定; 2）与对照组相比，在gelsolin转染的细胞中，Gelsolim表达增加，而PLC-β_1、PLC-γ_1和PLC-δ_1表达保持不变。各组间基础IP_3产生量无显著差异。与对照组相比，转染gelsolin的细胞在EGF刺激后IP_3的产生增加。这些结果表明，神经凝溶胶蛋白可能在PtcIns-PLC调节系统中发挥重要作用。少

Activation of phospholipase C (PLC) isoenzyme families through a G protein-mediated pathway has been widely indicated in many different cells and tissues. Whereas evidence for a G protein-dependent stimulation of PLC is abundant, reports on the inhibition of PLC through a G protein-mediated pathway have only recently started appearing. Moreover, it has been demonstrated that gelsolin (actin regulatory protein) has phosphatidylinositol (PtdIns) binding regions and has to be activated by Ca^<2+>. Although gelsolin is ubiquitous in normal mammalian tissues, relatively little is known about the role in neurological PtdIns-PLC systems. The present studies demonstrated (1) that rat cerebral-cortical membrane preparations retain G proteindependent inhibition of PLC activity and (2) the effect of gelsolin overexprssion on epidermal growth factor (EGF) receptor stimulation that mediates inositol 1,4,5-trisphosphate (IP_3) production in mouse neuroblastoma TBJ cells. Two diversity of functions a … More re attributed to PLC isozymes : 1) Our results indicate that nanomolar concentrations of guanine nucleotides in cerebral-cortical membranes promoted an inhibition of PLC activity and suggested that there may be dual effects of guanine nucleotides on the PLC system. Cerebral cortex membranes expressed a greater amount of PLC-beta_1 isoenzymes. Since PLC-beta_1 is the sffector for the G protein-mediated pathway, our studies suggest that the different G proteins regulate PLC activity through a shared mechanism that remains to be identified ; and 2) Gelsolim expression was increased in gelsolintransfected cells compared with controls, but PLC-beta_1, PLC-gamma_1 and PLC-delta_1 expression remained unchanged. No significant difference in the basal IP_3 production was observed between the groups. IP_3 production after stimulation with EGF was higher in gelsolin-transfected cells compared with controls. These result suggest that neurological gelsolin may play an important role in the PtcIns-PLC regulation systems. Less