SUBUNITS-BETA-GAMMA OF HETEROTRIMERIC G-PROTEIN ACTIVATE BETA-2 ISOFORM OF PHOSPHOLIPASE-C
SUBUNITS-BETA-GAMMA OF HETEROTRIMERIC G-PROTEIN ACTIVATE BETA-2 ISOFORM OF PHOSPHOLIPASE-C
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DOI：
10.1038/360686a0
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发表时间：
1992-12-17
期刊：
影响因子：
64.8
通讯作者：
SIMON, MI
中科院分区：
文献类型：
--
作者：
KATZ, A;WU, DQ;SIMON, MI
异源三聚体G蛋白的激活导致与α亚基结合的GDP交换为GTP，随后β和γ亚基的复合物（G（β γ））解离。不同G蛋白的α-亚基与各种效应子相互作用1 -7，但对游离G（β-γ）复合物的功能知之甚少。G（β-γ）与心脏钾通道8、视网膜磷脂酶A2（参考文献9）和特异性受体激酶10的激活有关，体外重建实验表明，G（β-γ）复合物可与G（α）亚基一起作用，调节腺苷酸环化酶不同亚型的活性11。在HL-60细胞提取物中可以分离的两种磷脂酶活性中，发现纯化的G（β-γ）激活其中之一12。 在这里，我们报告说，在共转染测定G（β-γ）亚基特异性激活β 2，而不是β 1亚型的磷脂酶，其作用于磷脂酰肌醇。我们使用转染试验也表明，受体介导的G（β-γ）从G蛋白，是敏感的百日咳毒素的释放可以导致磷脂酶的激活。这种效应可能是在某些细胞系统中观察到的百日咳毒素敏感性磷脂酶C激活的基础（综述见参考文献13和14）。
THE activation of heterotrimeric G proteins results in the exchange of GDP bound to the alpha-subunit for GTP and the subsequent dissociation of a complex of the beta- and gamma-subunits (G(betagamma)). The alpha-subunits of different G proteins interact with a variety of effectors1-7, but less is known about the function of the free G(betagamma) complex. G(betagamma) has been implicated in the activation of a cardiac potassium channel8, a retinal phospholipase A2 (ref. 9) and a specific receptor kinase10, and in vitro reconstitution experiments indicate that the G(betagamma) complex can act with G(alpha) subunit to modulate the activity of different isoforms of adenylyl cyclase11. Of two phospholipase activities that can be separated in extracts of HL-60 cells, purified G(betagamma) is found to activate one of them12. Here we report that in co-transfection assays G(betagamma) subunits specifically activate the beta2 and not the beta1 isoform of phospholipase, which acts on phosphatidylinositol. We use transfection assays to show also that receptor-mediated release of G(betagamma) from G proteins that are sensitive to pertussis toxin can result in activation of the phospholipase. This effect may be the basis of the pertussis-toxin-sensitive phospholipase C activation seen in some cell systems (reviewed in refs 13 and 14).