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

Title: Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms
Authors: Colucci, F
Rosmaraki, E
Bregenholt, S
Samson, SI
Di Bartolo, V
Turner, M
Vanes, L
Tybulewicz, V
Di Santo, JP
Item Type: Journal Article
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)-γ 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-γ 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-γ production.
Issue Date: 18-Jun-2001
Date of Acceptance: 15-May-2001
URI: http://hdl.handle.net/10044/1/58007
DOI: https://dx.doi.org/10.1084/jem.193.12.1413
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 1413
End Page: 1424
Journal / Book Title: Journal of Experimental Medicine
Volume: 193
Issue: 12
Copyright Statement: © 2001 The Rockefeller University Press
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
tumor clearance
Listeria infection
exocytosis
lymphoid development
cytokines
VAV PROTOONCOGENE PRODUCT
GTP EXCHANGE FACTOR
RECEPTOR TYROSINE KINASE
CHEDIAK-HIGASHI-SYNDROME
T-CELL
HEMATOPOIETIC-CELLS
GRANULE EXOCYTOSIS
MEDIATED CYTOTOXICITY
PROTEIN-KINASES
CROSS-LINKING
Animals
Antibody-Dependent Cell Cytotoxicity
Calcium
Cell Cycle Proteins
Cell Differentiation
Cells, Cultured
Cytotoxicity, Immunologic
Exocytosis
Interferon-gamma
Killer Cells, Natural
Listeriosis
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Neoplasms, Experimental
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-vav
Receptors, Immunologic
Signal Transduction
T-Lymphocytes
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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