作者
David T Dudley, Long Pang, Stuart J Decker, Alexander J Bridges, Alan R Saltiel
发表日期
1995/8/15
期刊
Proceedings of the National Academy of Sciences
卷号
92
期号
17
页码范围
7686-7689
简介
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 …
引用总数
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DT Dudley, L Pang, SJ Decker, AJ Bridges, AR Saltiel - Proceedings of the National Academy of Sciences, 1995