ISOZYME-SELECTIVE STIMULATION OF PHOSPHOLIPASE C-BETA-2 BY G-PROTEIN BETA-GAMMA-SUBUNITS
ISOZYME-SELECTIVE STIMULATION OF PHOSPHOLIPASE C-BETA-2 BY G-PROTEIN BETA-GAMMA-SUBUNITS
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DOI：
10.1038/360684a0
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发表时间：
1992-12-17
期刊：
影响因子：
64.8
通讯作者：
GIERSCHIK, P
中科院分区：
文献类型：
--
作者：
CAMPS, M;CAROZZI, A;GIERSCHIK, P
磷脂酶C （PLC）水解磷脂酰肌醇4,5-二磷酸是许多细胞外信号分子调节其靶细胞功能的关键机制1,2。至少有8种不同的PLC同工酶在哺乳动物细胞中被识别。受体控制的PLC通常由G蛋白调控，在某些细胞中，G蛋白可被百日咳毒素修饰，而在其他细胞中则不能。在后一种细胞中，PLC-beta1，而不是PLC-gamma1或PLC-delta1，可能被G蛋白α -亚单位的α (q)-亚家族成员激活7-10。在培养的人HL-60粒细胞的可溶部分中，一种未识别的PLC被从视网膜和大脑中纯化的G蛋白β - γ亚基特异性刺激11。在HL-60细胞cDNA文库中鉴定出第二个plc - β互补DNA (plc - β 2)，促使我们研究纯化的G蛋白β γ亚基对培养的哺乳动物细胞中瞬时表达的plc - β 1和plc - β 2活性的影响。我们在这里报道，plc - β 1和plc - β 2受到游离β - γ亚基的刺激，plc - β 2对β - γ刺激最敏感。因此，β - γ亚基对PLC的刺激是同工酶选择性的，PLC- β 2是β - γ刺激的主要目标。β γ亚基激活PLC- β 2可能是百日咳毒素敏感G蛋白刺激PLC的重要机制。
HYDROLYSIS by phospholipase C (PLC) of phosphatidylinositol 4,5-bisphosphate is a key mechanism by which many extracellular signalling molecules regulate functions of their target cells1,2. At least eight distinct isozymes of PLC are recognized in mammalian cells3,4. Receptor-controlled PLC is often regulated by G proteins, which can be modified by pertussis toxin in some cells but not in others5,6. In the latter cells, PLC-beta1, but not PLC-gamma1 or PLC-delta1, may be activated by members of the alpha(q)-subfamily of the G protein alpha-subunits7-10. An unidentified PLC in soluble fractions of cultured human HL-60 granulocytes is specifically stimulated by G protein betagamma subunits purified from retina and brain11. Identification of a second PLC-beta complementary DNA (PLC-beta2) in an HL-60 cell cDNA library9 prompted us to investigate the effect of purified G protein betagamma subunits on the activities of PLC-beta1 and PLC-beta2 transiently expressed in cultured mammalian cells. We report here that PLC-beta1 and PLC-beta2 were stimulated by free betagamma subunits and that PLC-beta2 was the most sensitive to betagamma stimulation. Thus stimulation of PLC by betagamma subunits is isozyme-selective and PLC-beta2 is a prime target of betagamma stimulation. Activation of PLC-beta2 by betagamma subunits may be an important mechanism by which pertussis toxin-sensitive G proteins stimulate PLC.