Finney R E, Robbins S M, Bishop J M
The George Williams Hooper Foundation, University of California, Box 0552, San Francisco, California 94143, USA.
Curr Biol. 1993 Dec 1;3(12):805-12. doi: 10.1016/0960-9822(93)90214-9.
A key pathway for transduction of proliferative, developmental and oncogenic stimuli from receptors at the cell surface to transcription factors located in the nucleus involves the activation of pRas and pRaf-1. Recent publications have described a physical interaction between pRas and pRaf-1, either as ectopic proteins in yeast or as recombinant proteins added to cellular extracts. Until now, however, physical complexes that include pRas and pRaf-1 have not been identified as native structures in mammalian cells.
We have directly identified a pRas-pRaf-1 complex in extracts of mammalian cells. Formation of the complex is augmented in neoplastically transformed cells expressing constitutively activated pRas. Moreover, the complexes form in concert with the activation of pRas during intracellular signalling through the T-cell receptor in T-leukemia cells.
We propose that, pRas signals to pRaf-1 in vivo by means of a direct physical interaction that results in activation of the pRaf-1 protein kinase.
从细胞表面受体向位于细胞核内的转录因子传导增殖、发育及致癌刺激的关键途径涉及pRas和pRaf-1的激活。最近的出版物描述了pRas和pRaf-1之间的物理相互作用,无论是作为酵母中的异位蛋白还是作为添加到细胞提取物中的重组蛋白。然而,到目前为止,包含pRas和pRaf-1的物理复合物尚未在哺乳动物细胞中被鉴定为天然结构。
我们已经在哺乳动物细胞提取物中直接鉴定出一种pRas-pRaf-1复合物。在表达组成型激活pRas的肿瘤转化细胞中,该复合物的形成增加。此外,在T白血病细胞中通过T细胞受体进行细胞内信号传导期间,复合物的形成与pRas的激活协同发生。
我们提出,pRas在体内通过直接的物理相互作用向pRaf-1发出信号,从而导致pRaf-1蛋白激酶的激活。