分化抑制了类似受体的蛋白质 - 铁酸酶-αα 的活性
1Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. gjiang@aim.salk.edu
Nature
|October 19, 1999
概括
分化在体内负面调节类似受体的蛋白质-铁酸酶α (RPTPalpha) 的活性. 这种调节在立体化学上与晶体结构一致,表明控制细胞生长和分化的机制.
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
- 生物化学 生物化学
背景情况:
- 蛋白氨酸酸酶 (PTPs) 对细胞过程至关重要.
- 类似受体的PTP (RPTP) 调节尚未完全理解.
- 晶体结构表明RPTPalpha二元化可能会抑制活性.
研究的目的:
- 通过二分化来研究全长RPTPalpha活动的体内调节.
- 为了确定二元化是否对RPTPalpha功能产生负面影响.
- 为了确认RPTPalpha二元化介导抑制的结构基础.
主要方法:
- 使用氨酸突变物产生稳定的二硫化物结合的RPTPalpha同型分子.
- 在RPTPalpha-null小鼠胚胎细胞中表达野生型和突变的RPTPalpha.
- 评估了c-Src Tyr 529的脱和活性.
主要成果:
- 经证明,二分化在体内抑制了全长的RPTPalpha活性.
- 特定的氨酸突变 (Phe135Cys,Thr141Cys) 启用了二分化和增加了c-Src活性.
- 突变抑制 (Pro210/211到Leu) 恢复了c-Src激活在一个二分化缺陷突变的突变.
结论:
- 在体内通过二分化,RPTPalpha活性可以被负面调节.
- 抑制机制与RPTPalpha的结构数据是一致的.
- 分化为细胞信号传输中的RPTPalpha提供了一个潜在的调节机制.
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