Phospholipase C : Diversity of isoenzyme functions and signal transduction.

通过G蛋白介导的途径激活磷脂酶C （PLC）同工酶家族已广泛应用于许多不同的细胞和组织。尽管G蛋白依赖性刺激PLC的证据丰富，但通过G蛋白介导的途径抑制PLC的报道直到最近才开始出现。此外，已经证明gelsolin（肌动蛋白调节蛋白）具有磷脂酰肌醇（PtdIns）结合区，并且必须被Ca^<2+>激活。虽然凝胶在正常哺乳动物组织中普遍存在，但对其在神经ptdin - plc系统中的作用知之甚少。目前的研究表明：(1)大鼠脑皮质膜制剂保留了对PLC活性的G蛋白不依赖性抑制；(2)gelsolin过表达对表皮生长因子（EGF）受体刺激的影响，介导小鼠神经母细胞瘤TBJ细胞中肌醇1,4,5-三磷酸（IP_3）的产生。PLC同工酶具有两种不同的功能：1)我们的研究结果表明，大脑皮层膜中纳摩尔浓度的鸟嘌呤核苷酸促进PLC活性的抑制，并表明鸟嘌呤核苷酸可能对PLC系统具有双重作用。大脑皮层膜表达大量的PLC-beta_1同工酶。由于PLC-beta_1是G蛋白介导途径的效应子，我们的研究表明，不同的G蛋白通过一种共享的机制调节PLC的活性，该机制尚待确定；2)与对照组相比，转染Gelsolim的细胞Gelsolim表达增加，但PLC-beta_1、PLC-gamma_1和PLC-delta_1表达不变。各组间基本IP_3产量无显著差异。EGF刺激后，gelsolin转染细胞的IP_3产量高于对照组。这些结果提示神经凝胶可能在PtcIns-PLC调控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