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哺乳动物的紫外线反应是由Src氨酸激酶的激活触发的
Y Devary1, R A Gottlieb, T Smeal
1Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636.
Cell
|December 24, 1992
概括
紫外线照射通过激活涉及Src氨酸激酶,Ha-Ras和Raf-1的信号级联来触发保护性细胞反应,最终增强转录因子AP-1的活动.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 对DNA损伤的反应反应
背景情况:
- 包括紫外线 (UV) 辐射在内的DNA损伤剂,激活哺乳动物细胞中的细胞反应.
- 这种反应涉及转录因子AP-1,这是Jun和Fos蛋白质的复合体.
- 了解启动这种紫外线反应的精确分子机制至关重要.
研究的目的:
- 阐明紫外线辐射诱导c-jun基因的信号通路.
- 识别UV响应中的关键分子参与者及其激活序列.
- 为了确定紫外线反应启动的细胞位置.
主要方法:
- 利用氨酸激酶抑制剂和v-src,Ha-ras和raf-1的主导阴性突变体来阻止特定的信号组件.
- 在紫外线暴露后研究了Src氨酸激酶,Ha-Ras和Raf-1的激活.
- 评估了细胞内谷氨水平对紫外线反应的影响.
主要成果:
- 紫外线照射激活Src氨酸激酶,其次是Ha-Ras和Raf-1激活,代表了最早的可检测步骤.
- 这些激酶或它们的突变体的抑制阻断了紫外线诱导的反应.
- 紫外线照射导致c-Jun的酸化增加,增强其转录活性.
- 紫外线反应受到细胞内谷氨水平升高的抑制,这表明氧化应激的作用.
- 紫外线反应似乎始于血,而不是核.
结论:
- 紫外线反应是由源于等离子体膜的信号级联启动的,涉及Src,Ras和Raf.
- 这一途径的高潮是转录因子AP-1 (c-Jun) 的激活,从而赋予了保护功能.
- 氧化应激可能在引起细胞对紫外线损伤的反应中发挥作用.
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