Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt
Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt
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DOI：
10.1126/science.286.5445.1738
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发表时间：
1999-11-26
期刊：
影响因子：
56.9
通讯作者：
Glass, DJ
中科院分区：
文献类型：
--
作者：
Rommel, C;Clarke, BA;Glass, DJ
细胞外信号通常导致Raf-MEK-ERK和PI 3 K-Akt途径的同时激活（其中ERK是细胞外调节的激酶，MEK是促分裂原活化蛋白激酶或ERK激酶，并且PI 3 K是磷脂酰肌醇3-激酶）。然而，这两种信号通路显示对肌细胞肥大产生相反的作用。此外，PI 3 K-Akt途径显示出抑制Raf-MEK-ERK途径：这种交叉调节依赖于细胞的分化状态：Akt活化抑制分化的肌管中的Raf-MEK-ERK途径，但不抑制其成肌细胞前体。Akt的阶段特异性抑制作用与其与Raf形成复合物的阶段特异性能力相关，表明存在抑制性Akt-Raf复合物的差异表达介质。
Extracellular signals often result in simultaneous activation of both the Raf-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kinase, MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is phosphatidylinositol 3-kinase). However, these two signaling pathways were shown to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI3K-Akt pathway was shown to inhibit the Raf-MEK-ERK pathway: this cross-regulation depended on the differentiation state of the cell: Akt activation inhibited the Raf-MEK-ERK pathway in differentiated myotubes, but not in their myoblast precursors. The stage-specific inhibitory action of Akt correlated with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Raf complex.