Document Detail


Rapamycin inhibits p34cdc2 expression and arrests T lymphocyte proliferation at the G1/S transition.
MedLine Citation:
PMID:  8109837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rapamycin, a potent immunosuppressant and antifungal agent, inhibits an evolutionarily conserved mechanism regulating cell cycle progression. In an interleukin-2 (IL-2) dependent murine T cell, we demonstrate that rapamycin arrested T cells prior to the entry into S-phase of the cell cycle and that rapamycin inhibited the IL-2-stimulated expression of p34cdc2, a serine/threonine kinase that is required for cells to progress through the cell cycle. The mechanism of action of rapamycin appeared specific since the structural analogue and immunosuppressant FK506 had no effect on the progression of the cells through S-phase or the expression of p34cdc2. These results demonstrate a rapamycin-sensitive IL-2-dependent signaling pathway in T cells and suggest that the immunosuppressive properties of rapamycin are mediated by impinging on the IL-2-induced T cell expression of p34cdc2.
Authors:
W M Flanagan; G R Crabtree
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  696     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1994-03-24     Completed Date:  1994-03-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  31-7     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Beckman Center, Stanford University Medical School, California 94025.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
G1 Phase / drug effects
Interleukin-2 / pharmacology
Lymphocyte Activation / drug effects*
Mice
Polyenes / pharmacology*
Protein-Serine-Threonine Kinases / biosynthesis*
S Phase / drug effects
Sirolimus
T-Lymphocytes / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Interleukin-2; 0/Polyenes; 53123-88-9/Sirolimus; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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