对于两个不同的功能,TOR激酶域是必需的,其中只有一个被拉帕米辛抑制
X F Zheng1, D Florentino, J Chen
1Howard Hughes Medical Institute Department of Chemistry, Harvard University Cambridge, Massachusetts 02138, USA.
Cell
|July 14, 1995
概括
涉及TOR1和TOR2蛋白质的拉巴胺素敏感通路调节细胞循环的进展. 激酶活性对G1功能至关重要,拉巴胺可以选择性地抑制这一过程.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 这种对拉巴胺素敏感的途径对于向细胞循环机械传输基信号至关重要,特别是对于G1阶段的进展.
- 在酵母中进行的遗传研究确定了TOR1和TOR2作为这一途径中的关键基因,假设它们是新型的酸氨基酶.
研究的目的:
- 调查TOR1和TOR2蛋白质中酶域的功能要求,以了解它们在G1细胞周期进展中的作用.
- 阐明FKBP12-拉巴胺素影响TOR蛋白功能的机制,特别是关于G1阶段和基本细胞过程.
主要方法:
- 对TOR1和TOR2基因突变的酵母菌株进行基因分析.
- 在各种条件下评估细胞循环进展 (G1) 和细胞生长,包括拉帕治疗.
- 对TOR蛋白的激酶和FKBP12-拉帕米辛结合域的功能性表征.
主要成果:
- 完整的激酶域对于TOR1和TOR2蛋白质的G1细胞周期功能至关重要.
- 突变的TOR1蛋白过度表达 (影响FKBP12-拉帕米辛结合域) 抑制了酵母细胞的生长.
- TOR2的基本功能需要一个完整的激酶域,但这种功能对拉帕米辛不敏感.
- 虽然两种TOR蛋白的G1功能对拉巴胺素敏感,但TOR2的基本功能不是.
结论:
- 托尔蛋白的激酶活性对于它们的G1细胞周期功能是不可或缺的.
- FKBP12-rapamycin不会广泛抑制TOR激酶活性,但可能会选择性地干扰效应因子相互作用或酸化.
- 这种选择性干扰表明TOR蛋白在细胞循环控制和基本细胞过程中的细微调节机制.
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