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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
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.
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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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