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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Blenis, John Cohen, Michael S. Shahbazian, David Roux, Philippe P. Sonenberg, Nahum Vu, Hieu Holz, Marina K. Taunton, Jack |
| Description | Author Affiliation: Roux PP ( Department of Pathology and Cell Biology, Institut de Recherche en Immunologie et en Cancérologie (IRIC), Université de Montréal, Montréal, Québec, Canada. philippe.roux@umontreal.ca) |
| Abstract | Converging signals from the mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) pathways are well established to modulate translation initiation. Less is known regarding the molecular basis of protein synthesis regulated by other inputs, such as agonists of the Ras/extracellular signal-regulated kinase (ERK) signaling cascade. Ribosomal protein (rp) S6 is a component of the 40S ribosomal subunit that becomes phosphorylated at several serine residues upon mitogen stimulation, but the exact molecular mechanisms regulating its phosphorylation and the function of phosphorylated rpS6 is poorly understood. Here, we provide evidence that activation of the p90 ribosomal S6 kinases (RSKs) by serum, growth factors, tumor promoting phorbol esters, and oncogenic Ras is required for rpS6 phosphorylation downstream of the Ras/ERK signaling cascade. We demonstrate that while ribosomal S6 kinase 1 (S6K1) phosphorylates rpS6 at all sites, RSK exclusively phosphorylates rpS6 at Ser(235/236) in vitro and in vivo using an mTOR-independent mechanism. Mutation of rpS6 at Ser(235/236) reveals that phosphorylation of these sites promotes its recruitment to the 7-methylguanosine cap complex, suggesting that Ras/ERK signaling regulates assembly of the translation preinitiation complex. These data demonstrate that RSK provides an mTOR-independent pathway linking the Ras/ERK signaling cascade to the translational machinery. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 19 |
| Volume Number | 282 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2007-05-11 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Mitogen-Activated Protein Kinase 1 Metabolism Mitogen-Activated Protein Kinase 3 Ribosomal Protein S6 Small-Conductance Calcium-Activated Potassium Channels Ras Proteins Cells, Cultured HeLa Cells Immunoblotting Immunoprecipitation Kidney Luciferases MAP Kinase Kinase Kinases Mutation Phosphorylation Polyribosomes Protein Biosynthesis RNA, Small Interfering Pharmacology Antagonists & Inhibitors Genetics Ribosomal Protein S6 Kinases, 90-kDa Ribosomes Signal Transduction Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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