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© Institut Pasteur
Macrophage apparaissant derrière un lymphocyte. Image colorisée.
Publication : The Journal of experimental medicine

Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of experimental medicine - 18 Jun 2001

Colucci F, Rosmaraki E, Bregenholt S, Samson SI, Di Bartolo V, Turner M, Vanes L, Tybulewicz V, Di Santo JP

Link to Pubmed [PMID] – 11413196

J. Exp. Med. 2001 Jun;193(12):1413-24

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 in vivo. 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 for Vav1 in NK cells: a role in cytotoxicity but not for IFN-gamma production.

http://www.ncbi.nlm.nih.gov/pubmed/11413196