PMID- 10576742 OWN - NLM STAT- MEDLINE DCOM- 19991214 LR - 20191210 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 286 IP - 5445 DP - 1999 Nov 26 TI - Phosphorylation and regulation of Raf by Akt (protein kinase B). PG - 1741-4 AB - 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. FAU - Zimmermann, S AU - Zimmermann S AD - Institute of Medical Virology, University of Zurich, Gloriastrasse 30/32, CH-8028 Zurich, Switzerland. FAU - Moelling, K AU - Moelling K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (CDKN1A protein, human) RN - 0 (Chromones) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (Cyclins) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Somatomedins) RN - 17885-08-4 (Phosphoserine) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.11.1 (AKT1 protein, human) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) RN - EC 3.6.5.2 (ras Proteins) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - *Cell Division MH - Cell Line MH - Chromones/pharmacology MH - Cyclin-Dependent Kinase Inhibitor p21 MH - Cyclins/metabolism MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Epidermal Growth Factor/pharmacology MH - Flavonoids/pharmacology MH - Humans MH - *MAP Kinase Signaling System MH - Morpholines/pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Phosphoserine/metabolism MH - Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism MH - Proto-Oncogene Proteins/antagonists & inhibitors/*metabolism MH - Proto-Oncogene Proteins c-akt MH - Proto-Oncogene Proteins c-raf/antagonists & inhibitors/*metabolism MH - Recombinant Fusion Proteins/metabolism MH - Signal Transduction MH - Somatomedins/pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Cells, Cultured MH - ras Proteins/metabolism EDAT- 1999/11/27 00:00 MHDA- 1999/11/27 00:01 CRDT- 1999/11/27 00:00 PHST- 1999/11/27 00:00 [pubmed] PHST- 1999/11/27 00:01 [medline] PHST- 1999/11/27 00:00 [entrez] AID - 8027 [pii] AID - 10.1126/science.286.5445.1741 [doi] PST - ppublish SO - Science. 1999 Nov 26;286(5445):1741-4. doi: 10.1126/science.286.5445.1741.