在非状元动物中,由构成性活跃的KSR3激活RAS独立的ERK
Aline Chessel1, Noémie De Crozé1, Maria Dolores Molina2
1Institut de Biologie Valrose CNRS, Université Côte d'Azur, Nice, France.
Nature communications
|July 5, 2023
概括
研究人员在海胚胎中发现了ERK信号激活的新机制,其中涉及一种新型蛋白质KSR3. 这一发现揭示了信号通路的演变,并有助于理解人类癌症突变.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- ERK信号传递对细胞发育至关重要,但其在海中皮质前体的激活机制是未知的.
- 现有的知识表明,细胞外连接体触发了ERK,但这在早期海的发育过程中没有观察到.
研究的目的:
- 为了阐明在海中皮质前体中ERK信号激活的细胞自主,RAS独立的机制.
- 为了确定参与调节早期胚胎发育期间ERK信号传递的新型蛋白质.
主要方法:
- 转录分析以确定参与ERK激活的基因.
- 遗传学分析,以追踪已识别的基因的进化历史.
- 在培养细胞中进行功能性测试,以测试已识别的蛋白质的活性.
主要成果:
- 发现了KSR3,一个蛋白质激活ERK信号转录,独立于RAS.
- KSR3属于许多无脊椎动物中发现的,但在和线虫中丢失的催化不活的RAF激活器家族.
- KSR3的结构类似于致癌的人类RAF突变,KSR3在培养细胞中独立于RAS激活ERK信号.
结论:
- KSR3家族蛋白质是无脊椎动物中RAS独立ERK信号的关键激活剂.
- 研究结果为ERK路径的演变提供了洞察力,并为其进化选择提供了机制.
- 确定了KSR3序列,以发现人类B-RAF中的激活突变,将无脊椎动物机制与人类癌症联系起来.
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