Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 41, Pages 14214-14221Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA120.015143
Keywords
ANXA5; PKC theta; NF-kappa B; T-cell activation; TCR; annexin; T-cell receptor (TCR); protein kinase C (PKC); T-cell biology; NF-kappa B (NF-KB)
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Funding
- Chinese National Natural Sciences Foundation [81630092, 81773099]
- National Key R&D Research Program, Ministry of Science and Technology [2017YFA0506002]
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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 PKC theta to the membrane, leading to NF-kappa B activation and thus transcription of relevant genes. However, the details of how PKC theta 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 PKC delta activation by interaction with PKC delta, a homologue of PKC theta, which implicates a potential role of ANXA5 involved in PKC theta signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKC theta to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKC theta 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-kappa B signaling in activated T cells. As a result, NF-kappa B 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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