Publication Date:
1997-07-04
Description:
The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunn, G J -- Hudson, C C -- Sekulic, A -- Williams, J M -- Hosoi, H -- Houghton, P J -- Lawrence, J C Jr -- Abraham, R T -- AR41189/AR/NIAMS NIH HHS/ -- DK28312/DK/NIDDK NIH HHS/ -- DK50628/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1997 Jul 4;277(5322):99-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9204908" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing
;
Androstadienes/pharmacology
;
Animals
;
Carrier Proteins/pharmacology
;
Cell Line
;
DNA-Binding Proteins/pharmacology
;
Eukaryotic Initiation Factor-4E
;
G1 Phase
;
Heat-Shock Proteins/pharmacology
;
Humans
;
Insulin/pharmacology
;
Peptide Initiation Factors/metabolism
;
Phosphoproteins/genetics/*metabolism
;
Phosphorylation
;
Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/*metabolism
;
Polyenes/*pharmacology
;
*Protein Kinases
;
Rats
;
Recombinant Proteins/metabolism
;
Repressor Proteins/genetics/*metabolism
;
Signal Transduction
;
Sirolimus
;
TOR Serine-Threonine Kinases
;
Tacrolimus Binding Proteins
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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