| First Author | Colucci F | Year | 2001 |
| Journal | J Exp Med | Volume | 193 |
| Issue | 12 | Pages | 1413-24 |
| PubMed ID | 11413196 | Mgi Jnum | J:70010 |
| Mgi Id | MGI:2136072 | Doi | 10.1084/jem.193.12.1413 |
| Citation | Colucci F, et al. (2001) Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms. J Exp Med 193(12):1413-24 |
| abstractText | 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. |
