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Raf-1在酵母中干扰Ras和Rap1A效应器功能。

Raf-1 interferes with Ras and Rap1A effector functions in yeast.

作者信息

Ruggieri R, Macdonald S G, Callow M, McCormick F

机构信息

Onyx Pharmaceuticals, Richmond, California.

出版信息

Mol Biol Cell. 1994 Feb;5(2):173-81. doi: 10.1091/mbc.5.2.173.

DOI:10.1091/mbc.5.2.173
PMID:8019003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC301023/
Abstract

Raf-1 is a serine/threonine kinase that acts downstream of Ras in mitogenic signal transduction pathways, but the mechanism by which Ras transmits signals to Raf-1 is not known. We have examined the interaction between Raf-1 and human H-ras in three different systems that utilize H-ras-induced phenotypes in Saccharomyces cerevisiae. In each system, the effects of H-ras depend on guanosine triphosphate and appear to be mediated through the H-ras effector binding region. H-ras effector function was blocked in each case by expression of the N-terminal regulatory domain of Raf-1. These inhibitory effects did not require the Raf-1 kinase domain. Raf-1 also blocked Rap1A effector function in S. cerevisiae. Raf-1, therefore, appears to interact with H-Ras and Rap1A in these in vivo systems with properties that suggest it is an immediate downstream effector.

摘要

Raf-1是一种丝氨酸/苏氨酸激酶，在有丝分裂信号转导途径中作用于Ras下游，但Ras将信号传递给Raf-1的机制尚不清楚。我们在利用酿酒酵母中H-ras诱导表型的三种不同系统中研究了Raf-1与人H-ras之间的相互作用。在每个系统中，H-ras的作用取决于三磷酸鸟苷，并且似乎是通过H-ras效应器结合区域介导的。在每种情况下，Raf-1的N端调节结构域的表达都会阻断H-ras效应器功能。这些抑制作用不需要Raf-1激酶结构域。Raf-1也阻断了酿酒酵母中的Rap1A效应器功能。因此，在这些体内系统中，Raf-1似乎与H-Ras和Rap1A相互作用，其特性表明它是直接的下游效应器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/3dc6e8047620/mbc00084-0055-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/4e10473c2e1e/mbc00084-0052-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/cea463ec48a2/mbc00084-0052-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/7f0a95a2d8bb/mbc00084-0053-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/0a6644bb5047/mbc00084-0054-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/033e219e3b4d/mbc00084-0054-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/838e/301023/3dc6e8047620/mbc00084-0055-a.jpg

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本文引用的文献

1
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Science. 1993 Jun 11;260(5114):1658-61. doi: 10.1126/science.8503013.
2
Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.表皮生长因子通过形成受体、Grb2衔接蛋白和Sos核苷酸交换因子的复合物来调节p21ras。
Cell. 1993 May 7;73(3):611-20. doi: 10.1016/0092-8674(93)90146-h.
3
Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling.
鉴定Ral的鸟嘌呤核苷酸解离刺激因子为R-ras、H-ras、K-ras和Rap的假定效应分子。
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12609-13. doi: 10.1073/pnas.91.26.12609.
鸟嘌呤核苷酸释放因子hSos1与Grb2结合，并将受体酪氨酸激酶与Ras信号传导联系起来。
Nature. 1993 May 6;363(6424):85-8. doi: 10.1038/363085a0.
4
The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.哺乳动物Grb2的SH2和SH3结构域将表皮生长因子（EGF）受体与Ras激活剂mSos1偶联起来。
Nature. 1993 May 6;363(6424):83-5. doi: 10.1038/363083a0.
5
Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation.Sos Ras交换蛋白与Grb2的关联涉及酪氨酸激酶信号转导和细胞转化。
Nature. 1993 May 6;363(6424):45-51. doi: 10.1038/363045a0.
6
A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.一种果蝇SH2-SH3衔接蛋白，参与将无翅酪氨酸激酶与Ras鸟嘌呤核苷酸交换激活剂Sos偶联。
Cell. 1993 Apr 9;73(1):179-91. doi: 10.1016/0092-8674(93)90170-u.
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An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.一种SH3-SH2-SH3蛋白是p21Ras1激活所必需的，并且在体外与七号less和Sos蛋白结合。
Cell. 1993 Apr 9;73(1):169-77. doi: 10.1016/0092-8674(93)90169-q.
8
Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro.体外Raf-1-MEK-ERK信号转导通路的重建。
Mol Cell Biol. 1993 Nov;13(11):6615-20. doi: 10.1128/mcb.13.11.6615-6620.1993.
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