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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6483
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pubmed:dateCreated |
1994-7-19
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pubmed:databankReference |
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pubmed:abstractText |
The structurally related natural products rapamycin and FK506 bind to the same intracellular receptor, FKBP12, yet the resulting complexes interfere with distinct signalling pathways. FKBP12-rapamycin inhibits progression through the G1 phase of the cell cycle in osteosarcoma, liver and T cells as well as in yeast, and interferes with mitogenic signalling pathways that are involved in G1 progression, namely with activation of the protein p70S6k (refs 5, 11-13) and cyclin-dependent kinases. Here we isolate a mammalian FKBP-rapamycin-associated protein (FRAP) whose binding to structural variants of rapamycin complexed to FKBP12 correlates with the ability of these ligands to inhibit cell-cycle progression. Peptide sequences from purified bovine FRAP were used to isolate a human cDNA clone that is highly related to the DRR1/TOR1 and DRR2/TOR2 gene products from Saccharomyces cerevisiae. Although it has not been previously demonstrated that either of the DRR/TOR gene products can bind the FKBP-rapamycin complex directly, these yeast genes have been genetically linked to a rapamycin-sensitive pathway and are thought to encode lipid kinases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Fungal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunophilins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Polyenes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/TOR1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/TOR2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
369
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pubmed:geneSymbol |
DRR1,
TOR1,
TOR2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
756-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8008069-Amino Acid Sequence,
pubmed-meshheading:8008069-Animals,
pubmed-meshheading:8008069-Carrier Proteins,
pubmed-meshheading:8008069-Cattle,
pubmed-meshheading:8008069-Cell Cycle Proteins,
pubmed-meshheading:8008069-Cell Line,
pubmed-meshheading:8008069-Cloning, Molecular,
pubmed-meshheading:8008069-DNA, Complementary,
pubmed-meshheading:8008069-Fungal Proteins,
pubmed-meshheading:8008069-G1 Phase,
pubmed-meshheading:8008069-Heat-Shock Proteins,
pubmed-meshheading:8008069-Humans,
pubmed-meshheading:8008069-Immunophilins,
pubmed-meshheading:8008069-Molecular Sequence Data,
pubmed-meshheading:8008069-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:8008069-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:8008069-Polyenes,
pubmed-meshheading:8008069-Proteins,
pubmed-meshheading:8008069-Recombinant Fusion Proteins,
pubmed-meshheading:8008069-Saccharomyces cerevisiae,
pubmed-meshheading:8008069-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:8008069-Sequence Homology, Amino Acid,
pubmed-meshheading:8008069-Sirolimus,
pubmed-meshheading:8008069-TOR Serine-Threonine Kinases,
pubmed-meshheading:8008069-Tacrolimus Binding Proteins
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pubmed:year |
1994
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pubmed:articleTitle |
A mammalian protein targeted by G1-arresting rapamycin-receptor complex.
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pubmed:affiliation |
Department of Chemistry, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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