Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt

Extracellular signals often result in simultaneous activation of both the R af-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kina se, MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is phos phatidylinositol 3-kinase). However, these two signaling pathways were show n to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI 3K-Akt pathway was shown to inhibit the Raf-MEK-ERK pathway: this cross-reg ulation depended on the differentiation state of the cell: Akt activation i nhibited the Raf-MEK-ERK pathway in differentiated myotubes, but not in the ir myoblast precursors. The stage-specific inhibitory action of Akt correla ted with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Ra f complex.