核酸交换因子Sos的膜准足以激活Ras信号通路
A Aronheim1, D Engelberg, N Li
1Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636.
Cell
|September 23, 1994
概括
将Sos蛋白向血是激活Ras信号通路的关键. 膜招募Sos,特别是在Ras附近,驱动瘤转化和通路刺激.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
- 瘤发生的发生因子.
背景情况:
- 增长因子受体的激活启动了涉及氨酸自酸化的信号级联.
- 像Grb2这样的SH2域含有蛋白质被招募到激活的受体.
- Grb2介导的Ras路径Sos激活的确切机制尚不清楚.
研究的目的:
- 研究膜招募在SOS介导的Ras通路激活中的作用.
- 为了确定Sos的等离子膜向是否足以激活Ras通路.
- 阐明SOS激活Ras信号的机制.
主要方法:
- 工程化Sos蛋白衍生物具有myristoylation或farnesylation信号用于血准.
- 评估了Ras信号通路的激活,包括ERK和AP-1活动.
- 利用哺乳动物细胞和酵母模型来研究SOS的功能.
- 生成的SOS衍生品缺少C终端区域.
主要成果:
- 索斯的myristoylation或farnesylation成功地将其向了血膜,刺激了Ras通路并导致瘤转化.
- 非功能性脂质修饰序列没有激活该途径.
- 膜向的SOS激活了酵母中的Ras信号.
- 缺少C端区域的SOS衍生物在两种细胞类型中都表现出显著增强的活性.
结论:
- 准Sos的等离子体膜,特别是在Ras附近,是Ras通路激活的主要驱动因素.
- 通过Sos C-终端区域缓解抑制可能代表二次激活机制.
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