TCR 诱导的、PKC-θ 介导的 NF-κB 激活受到 caspase-8-caspase-9-caspase-3 级联反应的调节。
TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8-caspase-9-caspase-3 cascade.
机构信息
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.
Section of Nephrology, Department of Medicine, The University of Chicago, IL 60637, United States.
出版信息
Biochem Biophys Res Commun. 2014 Jul 18;450(1):526-31. doi: 10.1016/j.bbrc.2014.06.010. Epub 2014 Jun 9.
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.
摘要
已有文献证明，凋亡过程中的关键蛋白 caspase-8 对于 TCR 介导的 NF-κB 激活也很重要。然而，其他的半胱天冬酶是否也参与了这一过程尚不清楚。在本报告中，我们发现除了 caspase-8，caspase-9 也参与了 TCR 介导的 NF-κB 激活。caspase-9 通过 caspase-3 依赖性方式诱导 PKC-θ 的激活、Bcl10 的磷酸化和 NF-κB 的激活，但 Bcl10 的磷酸化似乎与 NF-κB 的激活脱耦。此外，caspase-8 在 T 细胞激活过程中位于 caspase-9 的上游。因此，TCR 的交联引发了一个包含 caspase-8、caspase-9 和 caspase-3 的半胱天冬酶级联反应，该反应激活了 PKC-θ 依赖性途径，导致 NF-κB 的激活，以及与 PKC-θ 无关的 Bcl10 磷酸化，从而限制了 NF-kB 的活性。
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