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Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes
CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus–encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor–associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly b...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213302/ https://www.ncbi.nlm.nih.gov/pubmed/14981114 http://dx.doi.org/10.1084/jem.20031255 |
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author | Xie, Ping Hostager, Bruce S. Bishop, Gail A. |
author_facet | Xie, Ping Hostager, Bruce S. Bishop, Gail A. |
author_sort | Xie, Ping |
collection | PubMed |
description | CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus–encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor–associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines deficient in TRAF3 by homologous recombination. We found that CD40 signals were normal in the absence of TRAF3, with the exception of moderately enhanced c-Jun NH(2)-terminal kinase (JNK) activation and antibody secretion. In sharp contrast, LMP1 signaling was markedly defective in TRAF3(−/−) B cells. LMP1-induced activation of JNK and nuclear factor κB, up-regulation of CD23 and CD80, and antibody secretion were substantially affected by TRAF3 deficiency. Reconstitution of TRAF3 expression decreased CD40-induced JNK activation and antibody secretion, and fully restored LMP1 signaling. Although TRAF2 is widely believed to be important for LMP1 function, LMP1 signaling was intact in TRAF2(−/−) B cells. Our data reveal that CD40 and LMP1 unexpectedly use TRAF3 in different ways, and that TRAF3 is required for LMP1-mediated activation of B cells. |
format | Text |
id | pubmed-2213302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22133022008-03-11 Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes Xie, Ping Hostager, Bruce S. Bishop, Gail A. J Exp Med Article CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus–encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor–associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines deficient in TRAF3 by homologous recombination. We found that CD40 signals were normal in the absence of TRAF3, with the exception of moderately enhanced c-Jun NH(2)-terminal kinase (JNK) activation and antibody secretion. In sharp contrast, LMP1 signaling was markedly defective in TRAF3(−/−) B cells. LMP1-induced activation of JNK and nuclear factor κB, up-regulation of CD23 and CD80, and antibody secretion were substantially affected by TRAF3 deficiency. Reconstitution of TRAF3 expression decreased CD40-induced JNK activation and antibody secretion, and fully restored LMP1 signaling. Although TRAF2 is widely believed to be important for LMP1 function, LMP1 signaling was intact in TRAF2(−/−) B cells. Our data reveal that CD40 and LMP1 unexpectedly use TRAF3 in different ways, and that TRAF3 is required for LMP1-mediated activation of B cells. The Rockefeller University Press 2004-03-01 /pmc/articles/PMC2213302/ /pubmed/14981114 http://dx.doi.org/10.1084/jem.20031255 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 | Article Xie, Ping Hostager, Bruce S. Bishop, Gail A. Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title | Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title_full | Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title_fullStr | Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title_full_unstemmed | Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title_short | Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes |
title_sort | requirement for traf3 in signaling by lmp1 but not cd40 in b lymphocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213302/ https://www.ncbi.nlm.nih.gov/pubmed/14981114 http://dx.doi.org/10.1084/jem.20031255 |
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