| PMID : |
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 (18322174) |
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| titre : |
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Non-T Cell Activation Linker Promotes Mast Cell Survival by Dampening the Recruitment of SHIP1 by Linker for Activation of T Cells. |
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| auteur(s) : |
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Karine Roget1, Marie Malissen2, Odile Malbec1, Bernard Malissen2, Marc Daëron ( ) 1 |
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| laboratoire : |
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| résumé : |
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The linker for activation of T cells (LAT) and the non-T cell activation linker (NTAL) are two transmembrane adapters which organize IgE receptor (FcepsilonRI) signaling complexes in mast cells. LAT positively regulates, whereas NTAL negatively regulates mast cell activation. We previously found that the four distal tyrosines of LAT can generate negative signals. We show here that two of these tyrosines provide two binding sites for SHIP1, that LAT recruits SHIP1 in vivo, and that SHIP1 recruitment is enhanced in NTAL-deficient cells. We show that NTAL negatively regulates mast cell activation by decreasing the recruitment, by LAT, of molecules involved in FcepsilonRI-dependent positive signaling. We show that NTAL also decreases the recruitment of SHIP1 by LAT, leading to an increased phosphorylation of the antiapoptotic molecule Akt, and positively regulates mast cell survival. We finally show that the positive effect of NTAL on Akt phosphorylation and mast cell survival requires LAT. Our data thus document the mechanisms by which LAT and NTAL can generate both positive and negative signals which differentially regulate mast cell activation and survival. They also provide molecular bases for the recruitment of SHIP1 in FcepsilonRI signaling complexes. SHIP1 is a major negative regulator of mast cell activation and, hence, of allergic reactions. |
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| domaine : |
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Sciences du Vivant/Immunologie/Allergologie
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0022-1767 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| journal : |
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| Journal of Immunology (J Immunol) |
| Publisher |
American Association of Immunologists |
| ISSN |
0022-1767 |
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| Audience : |
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internationale |
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| date de publication : |
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15/03/2008 |
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| volume : |
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180 |
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| numéro : |
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6 |
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| page, identifiant, ... : |
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3689-3698 |
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| contrat, financement : |
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This work was supported by the Institut Pasteur, Inserm, the Fondation pour la Recherche Médicale (program Défis de la Recherche en Allergologie), and the Ministère de l'éducation Nationale, de la Recherche et de la Technologie. KR was financially supported by the Ministère de l'Education Nationale, de la Recherche et de la Technologie and by a Pasteur- Weizmann fellowship |
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