Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production

Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production
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正常 p21N-ras 将铃蟾肽和其他生长因子受体偶联到磷酸肌醇的产生

DOI:
10.1038/323173a0
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发表时间:
1986
期刊:
影响因子:
64.8
通讯作者:
A. Hall
A. Hall
中科院分区:
综合性期刊1区
文献类型:
--
作者:
M. Wakelam;S. Davies;M. Houslay;Ian McKay;C. Marshall;A. Hall

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许多受体响应配体激活,触发肌醇磷脂分解,导致快速的细胞内反应1 - 4。该通路的持续激活被认为是至少参与刺激细胞生长的因素之一,并且有许多推测4 - 6认为某些致癌基因使用该通路影响不受控制的细胞增殖。有人提出,与腺苷酸环酶的受体介导控制类似,肌醇磷脂代谢的受体刺激是通过称为Gp(或Np)的鸟嘌呤核苷酸调节蛋白(g蛋白)介导的。虽然这样的物种尚未被确定,但现在有强有力的实验证据表明,这一过程是由一种不同于刺激和抑制g蛋白(分别为Gs和Gi)的g蛋白介导的9-12。ras基因编码一种质膜蛋白p21,其唯一已知的生化特性是具有高亲和力的GTPase活性13。我们在这里表明,在NIH 3T3成纤维细胞中正常p21N-ras的表达导致某些生长因子受体偶联以刺激肌醇磷酸的产生。我们提出N-ras原癌基因编码一种蛋白质,该蛋白质将某些生长因子的受体偶联到磷脂酶c的刺激上,因此,N-ras p21可能是假定的Gp或功能相关蛋白。
Many receptors, in response to ligand activation, trigger inositol phospholipid breakdown, which leads to rapid intracellular responses1–4. The sustained activation of this pathway is believed to be at least one of the factors involved in the stimulation of cell growth and there has been much speculation4–6 that certain oncogenes use this pathway to effect uncontrolled cellular proliferation. It has been suggested7, by analogy with the receptor-mediated control of adenylate cyclase8, that the receptor stimulation of inositol phospholipid metabolism is mediated through a guanine nucleotide regulatory protein (G-protein) called Gp (or Np). Although such a species has not been identified, there is now strong experimental evidence that this process is mediated by a G-protein distinct from the stimulatory and inhibitory G-proteins (Gs and Gi, respectively)9–12. The ras genes code for a plasma membrane protein, p21, whose only known biochemical property is a high-affinity GTPase activity13. We show here that the expression of normal p21N–ras in NIH 3T3 fibroblasts leads to the coupling of certain growth factor receptors to stimulated inositol phosphate production. We propose that the N-ras proto-oncogene encodes a protein which couples the receptors for certain growth factors to the stimulation of phospholipase C. Thus, N-ras p 21 may be the putative Gp or a functionally related protein.
鸟嘌呤核苷酸刺激大鼠皮质膜中肌醇三磷酸的产生。
DOI: 10.1042/bj2320799
发表时间: 1985
期刊: The Biochemical journal
影响因子: --
作者:
Gonzales,RA;Crews,FT
通讯作者: Crews,FT
DOI: --
发表时间: 1985
期刊: The Journal of biological chemistry
影响因子: --
作者:
Litosch,I;Wallis,C;Fain,JN
通讯作者: Fain,JN