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RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation
Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis–associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Spl...
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/PMC2211984/ https://www.ncbi.nlm.nih.gov/pubmed/15280422 http://dx.doi.org/10.1084/jem.20040446 |
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author | Vivarelli, Marina S. McDonald, Douglas Miller, Mendy Cusson, Nicole Kelliher, Michelle Geha, Raif S. |
author_facet | Vivarelli, Marina S. McDonald, Douglas Miller, Mendy Cusson, Nicole Kelliher, Michelle Geha, Raif S. |
author_sort | Vivarelli, Marina S. |
collection | PubMed |
description | Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis–associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP(−/−) mice proliferated and underwent isotype switching normally in response to anti-CD40–IL-4 but completely failed to do so in response to LPS–IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP(−/−) splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase–Akt pathway. |
format | Text |
id | pubmed-2211984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22119842008-03-11 RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation Vivarelli, Marina S. McDonald, Douglas Miller, Mendy Cusson, Nicole Kelliher, Michelle Geha, Raif S. J Exp Med Brief Definitive Report Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis–associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP(−/−) mice proliferated and underwent isotype switching normally in response to anti-CD40–IL-4 but completely failed to do so in response to LPS–IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP(−/−) splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase–Akt pathway. The Rockefeller University Press 2004-08-02 /pmc/articles/PMC2211984/ /pubmed/15280422 http://dx.doi.org/10.1084/jem.20040446 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 Vivarelli, Marina S. McDonald, Douglas Miller, Mendy Cusson, Nicole Kelliher, Michelle Geha, Raif S. RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title | RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title_full | RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title_fullStr | RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title_full_unstemmed | RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title_short | RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation |
title_sort | rip links tlr4 to akt and is essential for cell survival in response to lps stimulation |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211984/ https://www.ncbi.nlm.nih.gov/pubmed/15280422 http://dx.doi.org/10.1084/jem.20040446 |
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