在NIH 3T3细胞中,通过Ras传递信号的机制方面
K Zhang1, A G Papageorge, D R Lowy
1Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892.
概括
增长因子通过刺激关氨酸核酸交换来增加活性Ras-GTP水平,而不是通过抑制GTPase激活蛋白,如GAP和神经纤维素 (NF1). 细胞密度也会影响Ras-GTP水平.
科学领域:
- 细胞信号通道是细胞信号通道.
- 分子生物学分子生物学
- 信号传导是指信号的传导方式.
背景情况:
- 拉斯蛋白是细胞信号传递的关键调节者.
- Ras的激活涉及与瓜诺辛三酸盐 (GTP) 的结合.
- 增长因素通过复杂的机制影响Ras活动.
研究的目的:
- 研究血清和生长因子调节Ras. Ras. GTP结合形式的机制.
- 确定关氨酸核酸交换和GTPase激活蛋白 (GAP) 活性在Ras调节中的作用.
主要方法:
- 在NIH 3T3细胞中过度表达野生类型和突变Ras蛋白 (His116).
- 用血清和血小板衍生生长因子 (PDGF) 治疗.
- 在不同细胞密度下测量与GTP结合的Ras水平.
主要成果:
- 血清和PDGF在表达正常Ras蛋白的细胞中增加了与GTP结合的Ras,但在表达快速交换His116突变的细胞中没有.
- 与高密度细胞相比,在低密度细胞中,与GTP结合的Ras水平更高.
- 高细胞密度与增加的GAP类活性相关.
结论:
- 增长因子主要刺激Ras上的关氨酸核酸交换.
- 在较高细胞密度下增加的GAP活性有助于降低Ras-GTP水平.
- 拉斯激活对mitogenic信号和细胞环境都很敏感.
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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.
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