Functional Dichotomy in Natural Killer Cell Signaling

• DOI: 10.1084/jem.193.12.1413
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Francesco Colucci; Eleftheria Rosmaraki; Søren Bregenholt; Sandrine I. Samson; Vincenzo Di Bartolo; Martin Turner; Lesley Vanes; Victor Tybulewicz; James P. Di Santo
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; CROSS-LINKING; Cytotoxicity; PROTEIN-KINASES; T-Lymphocytes; Cell Cycle Proteins; RECEPTOR TYROSINE KINASE; Research & Experimental Medicine; T-CELL; VAV PROTOONCOGENE PRODUCT; CHEDIAK-HIGASHI-SYNDROME; Mice; Immunologic; Neoplasms; Receptors; tumor clearance; Killer Cells; HEMATOPOIETIC-CELLS; Listeriosis; Receptors, Immunologic; Cells, Cultured; Mice, Knockout; Mitogen-Activated Protein Kinase 1; Cultured; Mitogen-Activated Protein Kinase 3; Research & Experimental; Cell Differentiation; 11 Medical And Health Sciences; Killer Cells, Natural; Medicine, Research & Experimental; Natural; Medicine; Listeria infection; Mitogen-Activated Protein Kinases; exocytosis; Life Sciences & Biomedicine; Signal Transduction; 570; lymphoid development; Cells; Knockout; Immunology; 610; Exocytosis; GRANULE EXOCYTOSIS; Experimental; Interferon-gamma; 03 medical and health sciences; Proto-Oncogene Proteins; GTP EXCHANGE FACTOR; Animals; Proto-Oncogene Proteins c-vav; Science & Technology; Antibody-Dependent Cell Cytotoxicity; Neoplasms, Experimental; cytokines; MEDIATED CYTOTOXICITY; Calcium

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