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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-24
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pubmed:abstractText |
Ligand-specific negative regulation of cytokine-induced signaling relies on down regulation of the cytokine receptors. Down regulation of the IFNAR1 sub-unit of the Type I interferon (IFN) receptor proceeds via lysosomal receptor proteolysis, which is triggered by ubiquitination that depends on IFNAR1 serine phosphorylation. While IFN-inducible phosphorylation, ubiquitination, and degradation requires the catalytic activity of the Tyk2 Janus kinase, here we found the ligand- and Tyk2-independent pathway that promotes IFNAR1 phosphorylation, ubiquitination, and degradation when IFNAR1 is expressed at high levels. A major cellular kinase activity that is responsible for IFNAR1 phosphorylation in vitro does not depend on either ligand or Tyk2 activity. Inhibition of ligand-independent IFNAR1 degradation suppresses cell proliferation. We discuss the signaling events that might lead to ubiquitination and degradation of IFNAR1 via ligand-dependent and independent pathways and their potential physiologic significance.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-10048764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-10321728,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-11070173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-11399767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-12554654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-14532120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-15021890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-15337770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-15371334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-15546383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-15753389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-16479007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-16551269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-7479980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-7524081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-7961637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8009221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8144546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8605876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8628273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8702790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-8910507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-9214631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-9501047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18166147-9914500
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1090-2104
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
7
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pubmed:volume |
367
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
388-93
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pubmed:dateRevised |
2011-3-18
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pubmed:meshHeading |
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pubmed:year |
2008
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pubmed:articleTitle |
Ligand-independent pathway that controls stability of interferon alpha receptor.
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pubmed:affiliation |
Department of Animal Biology and Mari Lowe Center for Comparative Oncology Research, School of Veterinary Medicine, University of Pennsylvania, Room 316 Hill Pavilion, 380 S University Avenue, Philadelphia, PA 19104-4539, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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