title: TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8-caspase-9-caspase-3 cascade.
abstract: 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.
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Hunan 41000, China; Department of Microbial Infection and Immunity, The Ohio State University, OH 43210, United States.
authors.forename: Yixia
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States.
authors.forename: Minxiang
authors.initials: M
authors.lastname: Lei
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States.
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States.
authors.forename: Guilin
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Hunan 41000, China. Electronic address: tianluny@163.com.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States; Department of Microbial Infection and Immunity, The Ohio State University, OH 43210, United States. Electronic address: jian.zhang@osumc.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes
chemical_list: D007527:Isoenzymes; D009097:Multienzyme Complexes; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D020169:Caspases
keywords: Caspase-9; NF-κB; T cell activation