Source:http://linkedlifedata.com/resource/pubmed/id/20147977
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2010-4-14
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| pubmed:abstractText |
SHIP-1 (SH2 (Src homology 2)-containing inositol 5'-phosphatase-1) functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by phosphoinositide-3 (PI 3)-kinase activity. As a result, SHIP-1 deficiency in mice results in myeloproliferation and B-cell lymphoma. On the other hand, SHIP-1-deficient mice have a reduced T-cell population, but the underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1 plays anti-apoptotic functions in T cells upon stimulation of the death receptor CD95/APO-1/Fas. Using primary T cells from SHIP-1(-/-) mice and T leukemic cell lines, we report that SHIP-1 is a potent inhibitor of CD95-induced death. We observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic reticulum (ER), in which it promotes CD95 glycosylation. This post-translational modification requires an intact SH2 domain of SHIP-1, but is independent of its phosphatase activity. The glycosylated CD95 fails to oligomerize upon stimulation, resulting in impaired death-inducing signaling complex (DISC) formation and downstream apoptotic cascade. These results uncover an unanticipated inhibitory function for SHIP-1 and emphasize the role of glycosylation in the regulation of CD95 signaling in T cells. This work may also provide a new basis for therapeutic strategies using compounds inducing apoptosis through the CD95 pathway on SHIP-1-negative leukemic T cells.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/inositol-1,4,5-trisphosphate...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
|
| pubmed:issn |
1476-5551
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| pubmed:author |
pubmed-author:AgostinisPP,
pubmed-author:ChariotAA,
pubmed-author:CharlierEE,
pubmed-author:CraigR BRB,
pubmed-author:DellAA,
pubmed-author:DeneubourgLL,
pubmed-author:Di ValentinEE,
pubmed-author:ErneuxCC,
pubmed-author:GloireGG,
pubmed-author:HaslamS MSM,
pubmed-author:PangP-CPC,
pubmed-author:PenningerJJ,
pubmed-author:PietteJJ,
pubmed-author:RahmouniSS,
pubmed-author:ZhangJJ
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
821-32
|
| pubmed:meshHeading |
pubmed-meshheading:20147977-Animals,
pubmed-meshheading:20147977-Antigens, CD95,
pubmed-meshheading:20147977-Apoptosis,
pubmed-meshheading:20147977-Blotting, Western,
pubmed-meshheading:20147977-Cells, Cultured,
pubmed-meshheading:20147977-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:20147977-Endoplasmic Reticulum,
pubmed-meshheading:20147977-Flow Cytometry,
pubmed-meshheading:20147977-Glycosylation,
pubmed-meshheading:20147977-Humans,
pubmed-meshheading:20147977-Lymphoma, T-Cell,
pubmed-meshheading:20147977-Mice,
pubmed-meshheading:20147977-Mice, Knockout,
pubmed-meshheading:20147977-Phosphoric Monoester Hydrolases,
pubmed-meshheading:20147977-Phosphorylation,
pubmed-meshheading:20147977-Protein Processing, Post-Translational,
pubmed-meshheading:20147977-RNA, Small Interfering,
pubmed-meshheading:20147977-Signal Transduction,
pubmed-meshheading:20147977-T-Lymphocytes
|
| pubmed:year |
2010
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| pubmed:articleTitle |
SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity.
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| pubmed:affiliation |
Grappe Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-Research, Signal Transduction Unit, Faculty of Sciences, University of Liège, Liège, Belgium.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|