Vav Regulates Peptide-specific Apoptosis in Thymocytes
The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymo...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212394/ https://www.ncbi.nlm.nih.gov/pubmed/9841924 |
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author | Kong, Young-Yun Fischer, Klaus-Dieter Bachmann, Martin F. Mariathasan, Sanjeev Kozieradzki, Ivona Nghiem, Mai P. Bouchard, Dennis Bernstein, Alan Ohashi, Pamela S. Penninger, Josef M. |
author_facet | Kong, Young-Yun Fischer, Klaus-Dieter Bachmann, Martin F. Mariathasan, Sanjeev Kozieradzki, Ivona Nghiem, Mai P. Bouchard, Dennis Bernstein, Alan Ohashi, Pamela S. Penninger, Josef M. |
author_sort | Kong, Young-Yun |
collection | PubMed |
description | The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav(−) (/−) thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28–mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca(2+) mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav(−) (/−) thymocytes. Vav was found to bind constitutively to PKC-θ in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform. |
format | Text |
id | pubmed-2212394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22123942008-04-16 Vav Regulates Peptide-specific Apoptosis in Thymocytes Kong, Young-Yun Fischer, Klaus-Dieter Bachmann, Martin F. Mariathasan, Sanjeev Kozieradzki, Ivona Nghiem, Mai P. Bouchard, Dennis Bernstein, Alan Ohashi, Pamela S. Penninger, Josef M. J Exp Med Articles The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav(−) (/−) thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28–mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca(2+) mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav(−) (/−) thymocytes. Vav was found to bind constitutively to PKC-θ in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform. The Rockefeller University Press 1998-12-07 /pmc/articles/PMC2212394/ /pubmed/9841924 Text en 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 | Articles Kong, Young-Yun Fischer, Klaus-Dieter Bachmann, Martin F. Mariathasan, Sanjeev Kozieradzki, Ivona Nghiem, Mai P. Bouchard, Dennis Bernstein, Alan Ohashi, Pamela S. Penninger, Josef M. Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title | Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title_full | Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title_fullStr | Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title_full_unstemmed | Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title_short | Vav Regulates Peptide-specific Apoptosis in Thymocytes |
title_sort | vav regulates peptide-specific apoptosis in thymocytes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212394/ https://www.ncbi.nlm.nih.gov/pubmed/9841924 |
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