NDLI: RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.

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RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.

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RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cohen, N. A. Barrow, R. K. Snyder, S. H. Burnett, P. E. Sabatini, D. M.
Description	Author Affiliation: Burnett PE ( Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.);
Abstract	The complex of rapamycin with its intracellular receptor, FKBP12, interacts with RAFT1/FRAP/mTOR, the in vivo rapamycin-sensitive target and a member of the ataxia telangiectasia mutated (ATM)-related family of kinases that share homology with the catalytic domain of phosphatidylinositol 3-kinase. The function of RAFT1 in the rapamycin-sensitive pathway and its connection to downstream components of the pathway, such as p70 S6 kinase and 4E-BP1, are poorly understood. Here, we show that RAFT1 directly phosphorylates p70(S6k), 4E-BP1, and 4E-BP2 and that serum stimulates RAFT1 kinase activity with kinetics similar to those of p70(S6k) and 4E-BP1 phosphorylation. RAFT1 phosphorylates p70(S6k) on Thr-389, a residue whose phosphorylation is rapamycin-sensitive in vivo and necessary for S6 kinase activity. RAFT1 phosphorylation of 4E-BP1 on Thr-36 and Thr-45 blocks its association with the cap-binding protein, eIF-4E, in vitro, and phosphorylation of Thr-45 seems to be the major regulator of the 4E-BP1-eIF-4E interaction in vivo. RAFT1 phosphorylates p70(S6k) much more effectively than 4E-BP1, and the phosphorylation sites on the two proteins show little homology. This raises the possibility that, in vivo, an unidentified kinase analogous to p70(S6k) is activated by RAFT1 phosphorylation and acts at the rapamycin-sensitive phosphorylation sites of 4E-BP1.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	95
Language	English
Publisher	National Academy of Sciences
Publisher Date	1998-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carrier Proteins Metabolism Phosphoproteins Phosphotransferases (Alcohol Group Acceptor) Ribosomal Protein S6 Kinases Adaptor Proteins, Signal Transducing Amino Acid Sequence DNA-Binding Proteins Eukaryotic Initiation Factor-4E Heat-Shock Proteins Molecular Sequence Data Peptide Initiation Factors Peptide Mapping Phosphorylation Phosphothreonine Polyenes Sirolimus TOR Serine-Threonine Kinases Tacrolimus Binding Proteins Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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