PMID- 20464435 OWN - NLM STAT- MEDLINE DCOM- 20110222 LR - 20211203 IS - 1438-2199 (Electronic) IS - 0939-4451 (Linking) VI - 39 IP - 5 DP - 2010 Nov TI - Evidence for cell cycle-dependent, rapamycin-resistant phosphorylation of ribosomal protein S6 at S240/244. PG - 1487-92 LID - 10.1007/s00726-010-0615-2 [doi] AB - The ribosomal protein S6 is essential for the formation of the subunits of higher eukaryotic ribosomes, and S6 heterozygosity leads to early embryonal lethality in mice. S6 is phosphorylated at clustered residues S235/236 and S240/244 upon numerous physiological and pathological stimuli. So far, the S6Kinases, S6K1 and S6K2 are the only proven S6 S240/244 phosphorylating enzymes in mammalian cells. The activity of these S6Kinases is strictly regulated via the mammalian target of rapamycin (mTOR) enzyme complex with raptor, named mTORC1. In time course experiments with the mTORC1 inhibitor rapamycin we here demonstrate rapamycin-resistant phosphorylation of the ribosomal protein S6 at S240/244. Serum-restimulation experiments further demonstrated that this rapamycin-resistant S6 240/244 phosphorylation is induced via serum factors in a cell cycle-dependent manner. Our data allow new insights into the regulation of S6 phosphorylation and provide evidence for the existence of rapamycin-resistant S6 phosphorylating kinase activities. FAU - Rosner, M AU - Rosner M AD - Institute of Medical Genetics, Medical University of Vienna, Wahringer Strasse 10, 1090, Vienna, Austria. FAU - Hengstschlager, M AU - Hengstschlager M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100513 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Multiprotein Complexes) RN - 0 (Proteins) RN - 0 (Ribosomal Protein S6) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Cell Cycle MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Humans MH - Mechanistic Target of Rapamycin Complex 1 MH - Multiprotein Complexes MH - Phosphorylation MH - Proteins/antagonists & inhibitors/metabolism MH - Ribosomal Protein S6/*antagonists & inhibitors/metabolism MH - Sirolimus/*pharmacology MH - Structure-Activity Relationship MH - TOR Serine-Threonine Kinases EDAT- 2010/05/14 06:00 MHDA- 2011/02/23 06:00 CRDT- 2010/05/14 06:00 PHST- 2010/04/26 00:00 [received] PHST- 2010/04/27 00:00 [accepted] PHST- 2010/05/14 06:00 [entrez] PHST- 2010/05/14 06:00 [pubmed] PHST- 2011/02/23 06:00 [medline] AID - 10.1007/s00726-010-0615-2 [doi] PST - ppublish SO - Amino Acids. 2010 Nov;39(5):1487-92. doi: 10.1007/s00726-010-0615-2. Epub 2010 May 13.