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CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1

The transcription factor NF-κB plays a key regulatory role in lymphocyte activation and generation of immune response. Stimulation of T cell receptor (TCR) induces phosphorylation of CARMA1 by PKCθ, resulting in formation of CARMA1-Bcl10-MALT1 (CBM) complex at lipid rafts and subsequently leading to...

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Autores principales: Sakamoto, Takashi, Kobayashi, Masayuki, Tada, Kohei, Shinohara, Masanobu, Io, Katsuhiro, Nagata, Kayoko, Iwai, Fumie, Takiuchi, Yoko, Arai, Yasuyuki, Yamashita, Kouhei, Shindo, Keisuke, Kadowaki, Norimitsu, Koyanagi, Yoshio, Takaori-Kondo, Akifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894987/
https://www.ncbi.nlm.nih.gov/pubmed/24465689
http://dx.doi.org/10.1371/journal.pone.0085762
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author Sakamoto, Takashi
Kobayashi, Masayuki
Tada, Kohei
Shinohara, Masanobu
Io, Katsuhiro
Nagata, Kayoko
Iwai, Fumie
Takiuchi, Yoko
Arai, Yasuyuki
Yamashita, Kouhei
Shindo, Keisuke
Kadowaki, Norimitsu
Koyanagi, Yoshio
Takaori-Kondo, Akifumi
author_facet Sakamoto, Takashi
Kobayashi, Masayuki
Tada, Kohei
Shinohara, Masanobu
Io, Katsuhiro
Nagata, Kayoko
Iwai, Fumie
Takiuchi, Yoko
Arai, Yasuyuki
Yamashita, Kouhei
Shindo, Keisuke
Kadowaki, Norimitsu
Koyanagi, Yoshio
Takaori-Kondo, Akifumi
author_sort Sakamoto, Takashi
collection PubMed
description The transcription factor NF-κB plays a key regulatory role in lymphocyte activation and generation of immune response. Stimulation of T cell receptor (TCR) induces phosphorylation of CARMA1 by PKCθ, resulting in formation of CARMA1-Bcl10-MALT1 (CBM) complex at lipid rafts and subsequently leading to NF-κB activation. While many molecular events leading to NF-κB activation have been reported, it is less understood how this activation is negatively regulated. We performed a cell-based screening for negative regulators of TCR-mediated NF-κB activation, using mutagenesis and complementation cloning strategies. Here we show that casein kinase-2 interacting protein-1 (CKIP-1) suppresses PKCθ-CBM-NF-κB signaling. We found that CKIP-1 interacts with CARMA1 and competes with PKCθ for association. We further confirmed that a PH domain of CKIP-1 is required for association with CARMA1 and its inhibitory effect. CKIP-1 represses NF-κB activity in unstimulated cells, and inhibits NF-κB activation induced by stimulation with PMA or constitutively active PKCθ, but not by stimulation with TNFα. Interestingly, CKIP-1 does not inhibit NF-κB activation induced by CD3/CD28 costimulation, which caused dissociation of CKIP-1 from lipid rafts. These data suggest that CKIP-1 contributes maintenance of a resting state on NF-κB activity or prevents T cells from being activated by inadequate signaling. In conclusion, we demonstrate that CKIP-1 interacts with CARMA1 and has an inhibitory effect on PKCθ-CBM-NF-κB signaling.
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spelling pubmed-38949872014-01-24 CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1 Sakamoto, Takashi Kobayashi, Masayuki Tada, Kohei Shinohara, Masanobu Io, Katsuhiro Nagata, Kayoko Iwai, Fumie Takiuchi, Yoko Arai, Yasuyuki Yamashita, Kouhei Shindo, Keisuke Kadowaki, Norimitsu Koyanagi, Yoshio Takaori-Kondo, Akifumi PLoS One Research Article The transcription factor NF-κB plays a key regulatory role in lymphocyte activation and generation of immune response. Stimulation of T cell receptor (TCR) induces phosphorylation of CARMA1 by PKCθ, resulting in formation of CARMA1-Bcl10-MALT1 (CBM) complex at lipid rafts and subsequently leading to NF-κB activation. While many molecular events leading to NF-κB activation have been reported, it is less understood how this activation is negatively regulated. We performed a cell-based screening for negative regulators of TCR-mediated NF-κB activation, using mutagenesis and complementation cloning strategies. Here we show that casein kinase-2 interacting protein-1 (CKIP-1) suppresses PKCθ-CBM-NF-κB signaling. We found that CKIP-1 interacts with CARMA1 and competes with PKCθ for association. We further confirmed that a PH domain of CKIP-1 is required for association with CARMA1 and its inhibitory effect. CKIP-1 represses NF-κB activity in unstimulated cells, and inhibits NF-κB activation induced by stimulation with PMA or constitutively active PKCθ, but not by stimulation with TNFα. Interestingly, CKIP-1 does not inhibit NF-κB activation induced by CD3/CD28 costimulation, which caused dissociation of CKIP-1 from lipid rafts. These data suggest that CKIP-1 contributes maintenance of a resting state on NF-κB activity or prevents T cells from being activated by inadequate signaling. In conclusion, we demonstrate that CKIP-1 interacts with CARMA1 and has an inhibitory effect on PKCθ-CBM-NF-κB signaling. Public Library of Science 2014-01-17 /pmc/articles/PMC3894987/ /pubmed/24465689 http://dx.doi.org/10.1371/journal.pone.0085762 Text en © 2014 Sakamoto et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sakamoto, Takashi
Kobayashi, Masayuki
Tada, Kohei
Shinohara, Masanobu
Io, Katsuhiro
Nagata, Kayoko
Iwai, Fumie
Takiuchi, Yoko
Arai, Yasuyuki
Yamashita, Kouhei
Shindo, Keisuke
Kadowaki, Norimitsu
Koyanagi, Yoshio
Takaori-Kondo, Akifumi
CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title_full CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title_fullStr CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title_full_unstemmed CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title_short CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1
title_sort ckip-1 is an intrinsic negative regulator of t-cell activation through an interaction with carma1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894987/
https://www.ncbi.nlm.nih.gov/pubmed/24465689
http://dx.doi.org/10.1371/journal.pone.0085762
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