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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2006-10-3
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pubmed:abstractText |
Although glucocorticoid (GC)-induced nongenomic effects have been reported, the underlying mechanisms remain unexplained. We previously described that lymphocyte-specific protein tyrosine kinase (LCK) and FYN oncogene related to SRC, FGR, YES (FYN) mediate GC-induced inhibition of T-cell-receptor (TCR) signalling. Here we characterize the underlying molecular mechanism. The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation. Experiments with cells transfected with GC-receptor short interfering RNA (siRNA) showed that the GC receptor is an essential component of the TCR signalling complex. Short-term GC treatment induces dissociation of this protein complex, resulting in impaired TCR signalling as a consequence of abrogated LCK/FYN activation. HSP90siRNA-transfected cells are not able to assemble this TCR-associated multiprotein complex, and accordingly HSP90siRNA treatment mimics GC effects on LCK/FYN activities. These observations support a model for nongenomic GC-induced immunosuppression on the basis of dissolution of membrane-bound GC-receptor multiprotein complexes after GC-receptor ligation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-10323679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-10793137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-10807665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-11283153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-11984591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-12117678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-12244567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-12614355,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-14718388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15242338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15265777,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15489916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15529366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15705806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15899916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-15922741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-16236742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-8648096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-8873614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16888650-9588727
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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/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/FYN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1469-221X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1023-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16888650-Antigens, CD4,
pubmed-meshheading:16888650-Cells, Cultured,
pubmed-meshheading:16888650-Dexamethasone,
pubmed-meshheading:16888650-Glucocorticoids,
pubmed-meshheading:16888650-HSP90 Heat-Shock Proteins,
pubmed-meshheading:16888650-Humans,
pubmed-meshheading:16888650-Leukocytes,
pubmed-meshheading:16888650-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:16888650-Models, Biological,
pubmed-meshheading:16888650-Multiprotein Complexes,
pubmed-meshheading:16888650-Protein Binding,
pubmed-meshheading:16888650-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:16888650-RNA, Small Interfering,
pubmed-meshheading:16888650-RNA Interference,
pubmed-meshheading:16888650-Receptors, Antigen, T-Cell,
pubmed-meshheading:16888650-Receptors, Glucocorticoid,
pubmed-meshheading:16888650-T-Lymphocytes,
pubmed-meshheading:16888650-Tissue Distribution,
pubmed-meshheading:16888650-Transfection
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pubmed:year |
2006
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pubmed:articleTitle |
Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN.
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pubmed:affiliation |
Laboratory of Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.lowenberg@amc.uva.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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