Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
1999; American Association for the Advancement of Science; Volume: 286; Issue: 5445 Linguagem: Inglês
10.1126/science.286.5445.1738
ISSN1095-9203
AutoresChristian Rommel, Brian Clarke, Sven Zimmermann, Lorna Nuñez, Roni Rossman, Kristina Reid, Karin Moelling, George D. Yancopoulos, David J. Glass,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoExtracellular 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.
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