| Stable activation of phosphatidylinositol 3-kinase in the T cell immunological synapse stimulates Akt signaling to FoxO1 nuclear exclusion and cell growth control. | |
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MedLine Citation:
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PMID: 15778376 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously reported at the single cell level that PI3K is activated after conjugate formation between T lymphocytes and APCs. However, in contrast to cells exposed to an asymmetrical signal that usually increase 3'-phosphoinositides (3'-PI) transiently in the region of the activated receptors, T cells contacting APC accumulate 3'-PI across their whole plasma membrane far beyond the region of the immunological synapse (IS). Importantly, this effect is maintained over time, for hours, and although PI3K-dependent pathways translate in various cell types extracellular stimuli into a wide range of biological events, in primary T cells this stability is mostly required for cell division induced by Ag. Using imaging methodologies, the present article elucidates the molecular mechanisms responsible for this particular functioning of the PI3K pathway in primary human T lymphocytes interacting with APCs, especially with dendritic cells. The results reveal that the IS unremittingly recruits PI3K to maintain high 3'-PI levels in T cells through phosphotyrosine-dependent mechanisms, suggesting a major participation of class Ia PI3K. This persistent activation of PI3K results in the Akt-dependent sequestration of the FoxO transcription factor, FoxO1, outside the nucleus of T cells interacting with APCs. Using an active form of FoxO1, we demonstrate that this compartmentalization process can affect T cell growth after Ag recognition. We conclude that the need for sustained PI3K signaling within the consolidated IS is probably an undemanding tactic used by primary T cells critical for initiating cell cycle progression through the prolonged inactivation of FoxO1, one important factor that can control cell quiescence. |
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Authors:
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Stéphanie Fabre; Valérie Lang; Julie Harriague; Aude Jobart; Terry G Unterman; Alain Trautmann; Georges Bismuth |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 174 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-21 Completed Date: 2005-06-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4161-71 Citation Subset: AIM; IM |
Affiliation:
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Département de Biologie Cellulaire, Institut Cochin, Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique, Université René Descartes, Paris, France. |
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism* Active Transport, Cell Nucleus Antigen-Presenting Cells Cell Communication Cell Proliferation* DNA-Binding Proteins / metabolism* Enzyme Activation Forkhead Transcription Factors Humans Phosphatidylinositol Phosphates / metabolism Protein Transport Protein-Serine-Threonine Kinases / physiology* Proto-Oncogene Proteins / physiology* Proto-Oncogene Proteins c-akt Signal Transduction T-Lymphocytes / enzymology*, immunology* Transcription Factors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK41430/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/FOXO1 protein, human; 0/Forkhead Transcription Factors; 0/Phosphatidylinositol Phosphates; 0/Proto-Oncogene Proteins; 0/Transcription Factors; 0/phosphatidylinositol 3,4,5-triphosphate; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.1.37/AKT1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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