Ablation of G(o) alpha-subunit results in a transformed phenotype and constitutively active phosphatidylcholine-specific phospholipase C
Ablation of G(o) alpha-subunit results in a transformed phenotype and constitutively active phosphatidylcholine-specific phospholipase C
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DOI：
10.1074/jbc.272.28.17312
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发表时间：
1997-07-11
影响因子：
4.8
通讯作者：
Raben, DM
中科院分区：
文献类型：
--
作者：
Cheng, J;Weber, JD;Raben, DM
Modulation of the components involved in mitogenic signaling cascades is critical to the regulation of cell growth. GTP-binding proteins and the stimulation of phosphatidylcholine (PC) hydrolysis have been shown to play major roles in these cascades, One of the enzymes involved in PC hydrolysis, a PC-specific phospholipase C (PC-PLC) has received relatively little attention, In this paper we examined the role of a particular heterotrimeric GTP-binding protein, G(o), in the regulation of cell growth and PC-PLC-mediated hydrolysis of PC in IIC9 fibroblasts. The G(o) alpha-subunit was ablated in IIC9 cells by stable expression of antisense RNA, These stably transfected cells acquired a transformed phenotype as indicated by: (a) the formation of multiple foci in monolayer cultures, (b) the acquisition of anchorage-independent growth in soft agar; and (c) an increased level of thymidine incorporation in the absence of added mitogens. These data implicate G(o) alpha as a novel tumor suppressor, Interestingly, PC-PLC activity was constitutively active in the G(o) alpha-ablated cells as evidenced by the chronically elevated levels of diacylglycerol and phosphorylcholine in the absence of growth factors, In contrast, basal activities of PG-phospholipase D, phospholipase A(2), or phosphoinositol-PLC were not affected, These data demonstrate, for the first time, a role for G(o) in regulating cell growth and provide definitive evidence for the existence of a PC-PLC in eukaryotic cells, The data further indicate that a subunit of G(o), is involved is regulating this enzyme.
