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Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity
Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif–containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries o...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211968/ https://www.ncbi.nlm.nih.gov/pubmed/15365099 http://dx.doi.org/10.1084/jem.20031847 |
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author | Cella, Marina Fujikawa, Keiko Tassi, Ilaria Kim, Sunjin Latinis, Kevin Nishi, Shinzo Yokoyama, Wayne Colonna, Marco Swat, Wojciech |
author_facet | Cella, Marina Fujikawa, Keiko Tassi, Ilaria Kim, Sunjin Latinis, Kevin Nishi, Shinzo Yokoyama, Wayne Colonna, Marco Swat, Wojciech |
author_sort | Cella, Marina |
collection | PubMed |
description | Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif–containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries out a key role in activation. However, whether Vav1 regulates only some or all NK cell–activating pathways is matter of debate. It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation. Here, we examine the relative contribution of each of these exchange factors to NK cell–mediated cytotoxicity using mice lacking one, two, or all three Vav proteins. We found that Vav1 deficiency is sufficient to disrupt DAP10-mediated cytotoxicity, whereas lack of Vav2 and Vav3 profoundly impairs FcRγ- and DAP12-mediated cytotoxicity. Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity. |
format | Text |
id | pubmed-2211968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22119682008-03-11 Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity Cella, Marina Fujikawa, Keiko Tassi, Ilaria Kim, Sunjin Latinis, Kevin Nishi, Shinzo Yokoyama, Wayne Colonna, Marco Swat, Wojciech J Exp Med Brief Definitive Report Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif–containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries out a key role in activation. However, whether Vav1 regulates only some or all NK cell–activating pathways is matter of debate. It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation. Here, we examine the relative contribution of each of these exchange factors to NK cell–mediated cytotoxicity using mice lacking one, two, or all three Vav proteins. We found that Vav1 deficiency is sufficient to disrupt DAP10-mediated cytotoxicity, whereas lack of Vav2 and Vav3 profoundly impairs FcRγ- and DAP12-mediated cytotoxicity. Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity. The Rockefeller University Press 2004-09-20 /pmc/articles/PMC2211968/ /pubmed/15365099 http://dx.doi.org/10.1084/jem.20031847 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Cella, Marina Fujikawa, Keiko Tassi, Ilaria Kim, Sunjin Latinis, Kevin Nishi, Shinzo Yokoyama, Wayne Colonna, Marco Swat, Wojciech Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title | Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title_full | Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title_fullStr | Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title_full_unstemmed | Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title_short | Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity |
title_sort | differential requirements for vav proteins in dap10- and itam-mediated nk cell cytotoxicity |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211968/ https://www.ncbi.nlm.nih.gov/pubmed/15365099 http://dx.doi.org/10.1084/jem.20031847 |
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