化学
丝裂原活化蛋白激酶
蛋白激酶A
丝裂原活化蛋白激酶激酶
MAP激酶激酶激酶
细胞周期蛋白依赖激酶2
ASK1
细胞周期蛋白依赖激酶9
地图2K7
c-Raf公司
作者
David T. Dudley,Long Pang,Stuart J. Decker,Alexander J. Bridges,Alan R. Saltiel
标识
DOI:10.1073/pnas.92.17.7686
摘要
Treatment of cells with a variety of growth factors triggers a phosphorylation cascade that leads to activation of mitogen-activated protein kinases (MAPKs, also called extracellular signal-regulated kinases, or ERKs). We have identified a synthetic inhibitor of the MAPK pathway. PD 098059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one] selectively inhibited the MAPK-activating enzyme, MAPK/ERK kinase (MEK), without significant inhibitory activity of MAPK itself. Inhibition of MEK by PD 098059 prevented activation of MAPK and subsequent phosphorylation of MAPK substrates both in vitro and in intact cells. Moreover, PD 098059 inhibited stimulation of cell growth and reversed the phenotype of ras-transformed BALB 3T3 mouse fibroblasts and rat kidney cells. These results indicate that the MAPK pathway is essential for growth and maintenance of the ras-transformed phenotype. Further, PD 098059 is an invaluable tool that will help elucidate the role of the MAPK cascade in a variety of biological settings.
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