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Titolo:
A perspective: Regulation of IgE receptor-mediated mast cell responses by a LAT-organized plasma membrane-localized signaling complex
Autore:
Rivera, J; Arudchandran, R; Gonzalez-Espinosa, C; Manetz, TS; Xirasagar, S;
Indirizzi:
NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA NIAMSD Bethesda MDUSA 20892 ct Chem Immunol, NIH, Bethesda, MD 20892 USA
Titolo Testata:
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
fascicolo: 1-3, volume: 124, anno: 2001,
pagine: 137 - 141
SICI:
1018-2438(200101/03)124:1-3<137:APROIR>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELL; TYROSINE PHOSPHORYLATION; IMMUNOGLOBULIN-E; ACTIVATION; VAV; TRANSDUCTION; AGGREGATION; MECHANISM; KINASES; DOMAIN;
Keywords:
mast cells; Fc epsilon RI; LAT; Vav; signal transduction; exocytosis; cytokines;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Rivera, J NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA NIAMSD Bethesda MD USA 20892 munol, NIH, Bethesda, MD 20892 USA
Citazione:
J. Rivera et al., "A perspective: Regulation of IgE receptor-mediated mast cell responses by a LAT-organized plasma membrane-localized signaling complex", INT A AL IM, 124(1-3), 2001, pp. 137-141

Abstract

Background: To understand how the high-affinity IgE receptor (Fc epsilon RI) communicates with downstream effecters, we focused on exploring the functional importance of the Fc epsilon RI-mediated formation and localization of a signaling complex that contains the hematopoietic cell-specific scaffolding protein linker for activation of T cells (LAT) and the guanine nucleotide exchange factor Vav1. Methods: Using the mast cell line RBL-2H3, we explored the localization of these proteins by confocal microscopy and cell fractionation. Additionally, the mechanism of function and the importance ofLAT and Vav1 to mast cells was studied in genetically disrupted mice and in mast cells derived from their bone marrow. Results: We found that LAT, Vav1 and the adapter molecule SLP-76 associated in detergent-resistant microdomains (lipid rafts) found in the plasma membrane upon Fc epsilon RI stimulation. In the absence of LAT, mast cells showed a remarkable loss of the secretory response and reduced cytokine responses. Vav1 deficiency also affected secretion, al though not to the extent of LAT deficiency, and inhibitedIL-2 and IFN-gamma production. LAT- and Vav1-deficient mice showed reducedblood histamine levels after a systemic anaphylaxis challenge as compared to their normal counterparts. Conclusions: The results demonstrate that LATis a central mediator in IgE receptor signaling by regulating multiple signaling pathways that affect mast cell degranulation and cytokine production. Vav1, a component of this LAT-containing signaling complex, regulates a specific subset of these responses. Copyright (C) 2001 S. Karger AG,Basel.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 23:37:54