Cargando…

GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10

Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine kinase involved in the regulation of various cellular functions, such as energy homoeostasis, cell growth and developmental processes. More recently, GSK3β has been identified as a part of a protein complex involved in...

Descripción completa

Detalles Bibliográficos
Autores principales: Abd-Ellah, Ali, Voogdt, Cornelia, Krappmann, Daniel, Möller, Peter, Marienfeld, Ralf B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777991/
https://www.ncbi.nlm.nih.gov/pubmed/29358699
http://dx.doi.org/10.1038/s41598-018-19822-z
_version_ 1783294266789855232
author Abd-Ellah, Ali
Voogdt, Cornelia
Krappmann, Daniel
Möller, Peter
Marienfeld, Ralf B.
author_facet Abd-Ellah, Ali
Voogdt, Cornelia
Krappmann, Daniel
Möller, Peter
Marienfeld, Ralf B.
author_sort Abd-Ellah, Ali
collection PubMed
description Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine kinase involved in the regulation of various cellular functions, such as energy homoeostasis, cell growth and developmental processes. More recently, GSK3β has been identified as a part of a protein complex involved in the regulation of the CARMA1-BCL10-MALT1 complex (CBM complex) formation, which is a key signalling event upon antigen receptor engagement of B and T cells, required for the activation of the NF-κB and JNK pathways. However, conflicting reports have been published regarding the role of GSK3β for the activation of the NF-κB signalling pathways. Therefore, we aimed to determine the impact of GSK3β on the NF-κB signalling induced upon T cell activation. Blocking GSK3β by either pharmacologic inhibitors (SB216763 and SB415286) or by RNAi caused a reduced proteolysis of the MALT1 targets CYLD1, BCL10 and RelB as well as diminished IκBα degradation, NF-κB DNA binding and NF-κB activity. This negative effect on NF-κB appears to be due to a diminished CBM complex formation caused by a reduced BCL10 phosphorylation. Taken together, we provide here evidence for a novel regulatory mechanism by which GSK3β affects NF-κB signalling in activated T cells.
format Online
Article
Text
id pubmed-5777991
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57779912018-01-31 GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10 Abd-Ellah, Ali Voogdt, Cornelia Krappmann, Daniel Möller, Peter Marienfeld, Ralf B. Sci Rep Article Glycogen synthase kinase 3β (GSK3β) is a ubiquitously expressed serine/threonine kinase involved in the regulation of various cellular functions, such as energy homoeostasis, cell growth and developmental processes. More recently, GSK3β has been identified as a part of a protein complex involved in the regulation of the CARMA1-BCL10-MALT1 complex (CBM complex) formation, which is a key signalling event upon antigen receptor engagement of B and T cells, required for the activation of the NF-κB and JNK pathways. However, conflicting reports have been published regarding the role of GSK3β for the activation of the NF-κB signalling pathways. Therefore, we aimed to determine the impact of GSK3β on the NF-κB signalling induced upon T cell activation. Blocking GSK3β by either pharmacologic inhibitors (SB216763 and SB415286) or by RNAi caused a reduced proteolysis of the MALT1 targets CYLD1, BCL10 and RelB as well as diminished IκBα degradation, NF-κB DNA binding and NF-κB activity. This negative effect on NF-κB appears to be due to a diminished CBM complex formation caused by a reduced BCL10 phosphorylation. Taken together, we provide here evidence for a novel regulatory mechanism by which GSK3β affects NF-κB signalling in activated T cells. Nature Publishing Group UK 2018-01-22 /pmc/articles/PMC5777991/ /pubmed/29358699 http://dx.doi.org/10.1038/s41598-018-19822-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Abd-Ellah, Ali
Voogdt, Cornelia
Krappmann, Daniel
Möller, Peter
Marienfeld, Ralf B.
GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title_full GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title_fullStr GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title_full_unstemmed GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title_short GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10
title_sort gsk3β modulates nf-κb activation and relb degradation through site-specific phosphorylation of bcl10
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777991/
https://www.ncbi.nlm.nih.gov/pubmed/29358699
http://dx.doi.org/10.1038/s41598-018-19822-z
work_keys_str_mv AT abdellahali gsk3bmodulatesnfkbactivationandrelbdegradationthroughsitespecificphosphorylationofbcl10
AT voogdtcornelia gsk3bmodulatesnfkbactivationandrelbdegradationthroughsitespecificphosphorylationofbcl10
AT krappmanndaniel gsk3bmodulatesnfkbactivationandrelbdegradationthroughsitespecificphosphorylationofbcl10
AT mollerpeter gsk3bmodulatesnfkbactivationandrelbdegradationthroughsitespecificphosphorylationofbcl10
AT marienfeldralfb gsk3bmodulatesnfkbactivationandrelbdegradationthroughsitespecificphosphorylationofbcl10