TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8–caspase-9–caspase-3 cascade

Yixia Zhao; Minxiang Lei; Zhaoyuan Wang; Guilin Qiao; Tianlun Yang; Jian Zhang

doi:10.1016/j.bbrc.2014.06.010

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TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8–caspase-9–caspase-3 cascade

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TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8–caspase-9–caspase-3 cascade

Yixia Zhao, Minxiang Lei, Zhaoyuan Wang, Guilin Qiao, Tianlun Yang and Jian Zhang

Biochemical and biophysical research communications, Vol.450(1), pp.526-531

07/18/2014

DOI: 10.1016/j.bbrc.2014.06.010

PMCID: PMC4107081

PMID: 24924627

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Abstract

•TCR-mediated NF-κB activation requires caspase-9.•Caspase-9 regulates Bcl10 phosphorylation and NF-κB activation in a caspase-3-dependent manner.•Caspase-8 lies upstream of caspase-9 during T cell activation. It has been documented that caspase-8, a central player in apoptosis, is also crucial for TCR-mediated NF-κB activation. However, whether other caspases are also involved this process is unknown. In this report, we showed that in addition to caspase-8, caspase-9 is required for TCR-mediated NF-κB activation. Caspase-9 induces activation of PKC-θ, phosphorylation of Bcl10 and NF-κB activation in a caspase-3-dependent manner, but it appears that Bcl10 phosphorylation is uncoupled from NF-κB activation. Furthermore, caspase-8 lies upstream of caspase-9 during T cell activation. Therefore, TCR ligation elicits a caspase cascade involving caspase-8, caspase-9 and caspase-3 which initiates PKC-θ-dependent pathway leading to NF-κB activation and PKC-θ-independent Bcl10 phosphorylation which limits NF-kB activity.

T cell activation

NF-κB

Caspase-9

Details

Title: Subtitle: TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8–caspase-9–caspase-3 cascade
Creators: Yixia Zhao - Department of Cardiology, Xiangya Hospital, Central South University, Hunan 41000, China
Minxiang Lei - Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States
Zhaoyuan Wang - Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States
Guilin Qiao - Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States
Tianlun Yang - Department of Cardiology, Xiangya Hospital, Central South University, Hunan 41000, China
Jian Zhang - Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.450(1), pp.526-531
DOI: 10.1016/j.bbrc.2014.06.010
PMID: 24924627
PMCID: PMC4107081
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AR049775, AI090901; name: Xiangya Hospital of Central South University
Language: English
Date published: 07/18/2014
Academic Unit: Pathology; IIHR--Hydroscience and Engineering
Record Identifier: 9984047742602771

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