Annexin A5 is essential for PKCθ translocation during T-cell activation
In: The Journal of biological chemistry, Jg. 295 (2020-07-09), Heft 41
Online
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Zugriff:
T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been reported to mediate PKCδ activation by interaction with PKCδ, a homologue of PKCθ, which implicates a potential role of ANXA5 involved in PKCθ signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKCθ to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKCθ upon TCR engagement and blocked the recruitment of CARMA1-BCL10-MALT1 signalosome, which provides a platform for the catalytic activation of IKKs and subsequent activation of canonical NF-κB signaling in activated T cells. As a result, NF-κB activation was impaired in ANXA5-KO T cells. T-cell activation was also suppressed by ANAX5 knockdown in primary T cells. These results demonstrated a novel role of ANXA5 in PKC translocation and PKC signaling during T-cell activation.
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Annexin A5 is essential for PKCθ translocation during T-cell activation
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Autor/in / Beteiligte Person: | Hua, Zi-Chun ; Wang, Xinran ; Huang, Yi ; Zhang, Xuerui ; Xu, Peipei ; Zhu, Banghui ; Li, Lin ; Hu, Zhaoqing ; Li, Maoxia ; Zhang, Jing ; Lin, Xiaolei |
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Zeitschrift: | The Journal of biological chemistry, Jg. 295 (2020-07-09), Heft 41 |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 1083-351X (print) |
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