在氨酸527上的c-Src被另一种蛋白质氨酸激酶酸化
J E Thomas1, P Soriano, J S Brugge
1Howard Hughes Medical Institute, Department of Microbiology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
概括
细胞Src蛋白激酶活性是通过酸化在氨酸527控制的. 这种调节是由另一种细胞蛋白氨酸激酶调节的,而不是Src自酸化.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 生物化学 生物化学
- 信号传输 信号传输
背景情况:
- 细胞Src (c-Src) 是一种非受体蛋白质氨酸激酶.
- c-Src活性是通过酸化调节的,特别是在527 (Tyr527) 氨酸残留物中,这抑制了其酶活性.
- 负责Tyr527酸化的特定激酶仍未确定,其中可能包括自酸化或外部激酶.
研究的目的:
- 为了确定Tyr527在c-Src中的酸化是否是一种自酸化事件,还是由另一种细胞激酶介导.
- 阐明c-Src激酶活性负调节的机制.
主要方法:
- 使用了一种修改后的c-Src形式,缺乏内在激酶活性.
- 在小鼠细胞中检查了Tyr527酸化,并对两种内源性Src等位基因 (Src-null细胞) 进行了有针对性的破坏.
- 在Src-null细胞中的Tyr527酸化水平与表达内源Src的细胞之间的比较.
主要成果:
- 在Tyr527上,非活性c-Src突变体的酸化发生在Src-null细胞和表达内源性Src的细胞中,水平相似.
- 这表明,除了c-Src本身之外,还有一种酶负责Tyr527的酸化.
结论:
- Tyr527的酸化是c-Src的关键抑制性修饰,由外部细胞蛋白氨酸激酶介导.
- 这一发现澄清了c-Src活动和它影响的细胞信号通路的关键调节机制.
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