Phosphorylation and Regulation of Raf by Akt (Protein Kinase B)

作者：Sven Zimmermann, Karin Moelling · 发表于：Science · 年份：1999 · DOI：10.1126/science.286.5445.1741 · 被引用次数：1092 · 研究领域：Cancer Mechanisms and Therapy、FOXO transcription factor regulation、PI3K/AKT/mTOR signaling in cancer

Activation of the protein kinase Raf can lead to opposing cellular responses such as proliferation, growth arrest, apoptosis, or differentiation. Akt (protein kinase B), a member of a different signaling pathway that also regulates these responses, interacted with Raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of Raf by Akt inhibited activation of the Raf-MEK-ERK signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt.