诱导NIH/3T3细胞的生长需要Raf-1蛋白激酶
W Kolch1, G Heidecker, P Lloyd
1Laboratory of Viral Carcinogenesis, NIH/NCI, Frederick Cancer Research and Development Center, Maryland 21702-1201.
Nature
|January 31, 1991
概括
Raf-1 激酶对于细胞生长信号传递至关重要. 抑制Raf-1功能阻断了增殖和转化,证实了其在生长因子受体和ras瘤基因下游的作用.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 瘤发生的发生因子.
背景情况:
- Raf-1蛋白激酶是增长因子介导信号传导的关键调节器.
- 它无处不在的表达和在增殖中的作用表明它在受体信号通路中的重要性.
研究的目的:
- 为了确定Raf-1激酶是否对血清和TPA调节的NIH/3T3细胞生长至关重要.
- 研究Raf-1在增长因子受体和瘤基因下游信号传导中的作用.
主要方法:
- 使用c-raf-1反意义RNA抑制Raf-1功能.
- 酶缺陷c-raf-1突变体 (craf301) 和调控域碎片 (HCR) 的表达.
- 评估由血清或TPA诱导的NIH/3T3细胞增殖和DNA复制.
主要成果:
- 对抗c-raf-1的反感性RNA干扰了NIH/3T3细胞增殖,并逆转了RAF转化细胞.
- 通过反感性RNA或酶缺陷突变体抑制Raf-1功能,阻断由血清,TPA和ras瘤基因诱导的增殖和转化.
- 降低的Raf蛋白水平与减少的DNA复制相关.
结论:
- 在由血清生长因子受体,蛋白质激酶C和ras启动的途径中,Raf-1激酶作为一种重要的信号转换器起作用.
- Raf-1对于调解细胞对生长信号和瘤转化的反应至关重要.
相关概念视频
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...


