通过氨酸酸化对蛋白质氨酸-氨酸酸酶2A类型的调节
J Chen1, B L Martin, D L Brautigan
1Division of Biology and Medicine, Brown University, Providence, RI 02912.
Science (New York, N.Y.)
|August 28, 1992
概括
2A型蛋白酸酶 (PP2A) 能够使蛋白激酶失活. 在Tyr307上,PP2A通过氨酸激酶的酸化可以暂时禁用它,从而可能增强细胞信号传递.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 信号传输 信号传输
背景情况:
- 启动细胞生长的细胞外信号激活蛋白激酶级联.
- 蛋白激酶通过酸化和脱酸化来调节.
- 2A型蛋白酸酶 (PP2A) 是一种关键的酶,可以去酸化和禁用蛋白激酶.
研究的目的:
- 通过酸化来研究PP2A活动的调节.
- 为了确定酸化PP2A的特定激酶.
- 确定PP2A酸化对细胞信号传输的功能后果.
主要方法:
- 在试验室中使用纯化的PP2A催化子单元进行酸化试验.
- 用酸酶抑制剂 (如奥卡酸) 治疗.
- 使用类腺三酸盐来制造一种抗自酸化的类酸化蛋白质.
- 使用质谱学识别酸化位点.
- 酶分析测量PP2A活动.
- 在体外激酶试验中,使用了各种类型的氨酸特异性蛋白激酶.
主要成果:
- PP2A的催化子单元由氨酸特异性蛋白激酶酸化.
- 酸化仅发生在氨酸残留物307 (Tyr307) 上.
- 观察到由p60v-src,p56lck,表皮生长因子受体和胰岛素受体等激酶的酸化.
- 当 thiophosphorylated 时,PP2A 活性显著降低 (> 90%),这表明自身酸化耐药性.
- 奥卡酸增强了酸化,这表明有自酸化成分.
- 作为一种机制,建议暂时停用PP2A.
结论:
- PP2A活性可以通过特定的氨酸激酶对Tyr307的酸化来暂时调节.
- 这种酸化事件导致PP2A活动的丧失.
- PP2A的暂时停活可能在调节激酶级联信号通路方面发挥作用.
- 了解PP2A调节提供了关于细胞生长和信号传输的见解.
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