Source:http://linkedlifedata.com/resource/pubmed/id/12165521
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2002-8-7
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pubmed:abstractText |
IFN-gamma contains a nuclear localization sequence that may play a role in the nuclear transport of activated STAT1alpha via a complex of IFN-gamma/IFN-gamma receptor (IFNGR)-1/STAT1alpha with the nuclear importer nucleoprotein interactor 1. In this study, we examine the mechanism of endocytosis of IFNGR-1 and the relationship of its nuclear translocation to that of STAT1alpha. In untreated WISH cells, both IFNGR-1 and IFNGR-2 were constitutively localized within caveolae-like microdomains isolated from plasma membrane. However, treatment of cells with IFN-gamma resulted in rapid migration of IFNGR-1, but not IFNGR-2, from these microdomains. Filipin pretreatment, which specifically inhibits endocytosis from caveolae-like microdomains, inhibited the nuclear translocation of IFN-gamma and IFNGR-1 as well as the tyrosine phosphorylation and nuclear translocation of STAT1alpha, but did not affect the binding of IFN-gamma to these cells. In the Jurkat T lymphocyte cell line, which does not express caveolin-1, nuclear translocation of IFNGR-1 and STAT1alpha were similarly inhibited by filipin pretreatment. Isolation of lipid microdomains from Jurkat cells showed that both IFNGR-1 and IFNGR-2 were associated with lipid microdomains only after stimulation with IFN-gamma, suggesting that the IFNGR subunits are recruited to lipid microdomains by IFN-gamma binding in lymphocytes (Jurkat) in contrast to their constitutive presence in epithelial (WISH) cells. In contrast, treatments that block clathrin-dependent endocytosis did not inhibit either activation or nuclear translocation of STAT1alpha or the nuclear translocation of IFN-gamma or IFNGR-1. Thus, membrane lipid microdomains play an important role in IFN-gamma-initiated endocytic events involving IFNGR-1, and the nuclear translocation of IFN-gamma, IFNGR-1, and STAT1alpha.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Filipin,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-Stimulated Gene Factor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/gamma interferon activation factor,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1959-69
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12165521-Active Transport, Cell Nucleus,
pubmed-meshheading:12165521-Binding Sites,
pubmed-meshheading:12165521-Cell Line,
pubmed-meshheading:12165521-Endocytosis,
pubmed-meshheading:12165521-Filipin,
pubmed-meshheading:12165521-Humans,
pubmed-meshheading:12165521-Interferon-Stimulated Gene Factor 3,
pubmed-meshheading:12165521-Interferon-gamma,
pubmed-meshheading:12165521-Membrane Microdomains,
pubmed-meshheading:12165521-Phosphorylation,
pubmed-meshheading:12165521-Receptors, Interferon,
pubmed-meshheading:12165521-Recombinant Proteins,
pubmed-meshheading:12165521-Signal Transduction,
pubmed-meshheading:12165521-Transcription Factors
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pubmed:year |
2002
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pubmed:articleTitle |
Lipid microdomains are required sites for the selective endocytosis and nuclear translocation of IFN-gamma, its receptor chain IFN-gamma receptor-1, and the phosphorylation and nuclear translocation of STAT1alpha.
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pubmed:affiliation |
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA. prem@ufl.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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