小型GTP结合蛋白Rac1和Cdc42调节JNK/SAPK信号通路的活性
O A Coso1, M Chiariello, J C Yu
1Molecular Signaling Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell
|June 30, 1995
概括
Rac1和Cdc42 GTPases是c-Jun氨基终端激酶 (JNK) 信号传递的关键调节者. 这些与Rho相关的蛋白质激活JNK,与Ras不同,对JNK对细胞因子和生长因子的反应至关重要.
科学领域:
- 细胞信号通道是细胞信号通道.
- 分子生物学分子生物学
- 信号传导是指信号的传导方式.
背景情况:
- c-Jun氨基末端激酶 (JNKs) 和基激活蛋白激酶 (MAPKs) 是相关的,但独立调节的信号通路.
- 虽然已知将生长因子与MAPKs联系在一起的途径,但对JNK激活的调节仍然不太了解.
研究的目的:
- 研究Ras和Rho相关GTPases (Rac1,Cdc42) 在调节JNK和MAPK激活中的作用.
- 为了识别选择性控制JNK活动的信号分子.
主要方法:
- 在COS-7细胞中激活Ras,Rac1和Cdc42GTPases的表达.
- 利用瘤性关氨酸核酸交换因子 (GEFs) 换取与Rho相关的蛋白质.
- 使用与Rho相关的GTPases的抑制分子和主导阴性突变.
主要成果:
- 激活的Ras刺激了MAPK,但没有JNK活动.
- 激活的Rac1和Cdc42GTPases在没有影响MAPK的情况下强烈激活了JNK.
- 对Rac1/Cdc42选择性刺激JNK活动的致癌GEF.
- 抑制剂和Rac1/Cdc42的主导阴性突变体阻断了GEF,细胞因子和生长因子的JNK激活.
结论:
- Rac1和Cdc42 GTPases在控制JNK信号通路方面发挥着至关重要的作用.
- 这些发现强调了与MAPK途径相比,JNK的独特调节机制.
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