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Titolo:
Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms
Autore:
Colucci, F; Rosmaraki, E; Bregenholt, S; Samson, SI; Di Bartolo, V; Turner, M; Vanes, L; Tybulewicz, V; Di Santo, JP;
Indirizzi:
Inst Pasteur, Lab Cytokines & Lymphoid Dev, Dept Immunol, F-75015 Paris, France Inst Pasteur Paris France F-75015 v, Dept Immunol, F-75015 Paris, France Inst Pasteur, Lab Mol Immunol, F-75015 Paris, France Inst Pasteur Paris France F-75015 Lab Mol Immunol, F-75015 Paris, France Babraham Inst, Cambridge CB2 4AT, England Babraham Inst Cambridge England CB2 4AT Inst, Cambridge CB2 4AT, England Natl Inst Med Res, London NW7 1AA, England Natl Inst Med Res London England NW7 1AA ed Res, London NW7 1AA, England
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 12, volume: 193, anno: 2001,
pagine: 1413 - 1424
SICI:
0022-1007(20010618)193:12<1413:FDINKC>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
VAV PROTOONCOGENE PRODUCT; GTP EXCHANGE FACTOR; RECEPTOR TYROSINE KINASE; CHEDIAK-HIGASHI-SYNDROME; T-CELL; HEMATOPOIETIC-CELLS; GRANULE EXOCYTOSIS; MEDIATED CYTOTOXICITY; PROTEIN-KINASES; CROSS-LINKING;
Keywords:
tumor clearance; Listeria infection; exocytosis; lymphoid development; cytokines;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Colucci, F Inst Pasteur, Lab Cytokines & Lymphoid Dev, Dept Immunol, 25 Rue Dr Roux, F-75015 Paris, France Inst Pasteur 25 Rue Dr Roux Paris France F-75015 Paris, France
Citazione:
F. Colucci et al., "Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms", J EXP MED, 193(12), 2001, pp. 1413-1424

Abstract

The product of the protooncogene Vav1 participates in multiple signaling pathways and is a critical regulator of antigen-receptor signaling in B and T lymphocytes, but its role during in vivo natural killer (NK) cell differentiation is not known. Here we have studied NK cell development in Vav1(-/-) mice and found that, in contrast to T and NK-T cells, the absolute numbers of phenotypically mature NK cells were not reduced. Vav1(-/-) mice produced normal amounts of interferon (IFN)-gamma in response to Listeria monocytogenes and controlled early infection but showed reduced tumor clearance invivo. In vitro stimulation of surface receptors in Vav1(-/-) NK cells resulted in normal IFN-gamma production but reduced tumor cell lysis. Vav1 was found to control activation of extracellular signal-regulated kinases and exocytosis of cytotoxic granules. In contrast, conjugate formation appeared to be only mildly affected, and calcium mobilization was normal in Vav1(-/-) NK cells. These results highlight fundamental differences between proximal signaling events in T and NK cells and suggest a functional dichotomy forVav1 in NK cells: a role in cytotoxicity but not for IFN-gamma production.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 20:02:02