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TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation

Nature Immunology volume 16, pages 11951203 (2015) | Download Citation

Abstract

Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxβ as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.

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Acknowledgements

We thank W.-L. Hu for assistance with the preparation of primary human CD4+ T cells; A. Balancio for animal assistance; C.-y. Wu for sharing experience with experiments with peripheral blood mononuclear cells; and former and current laboratory members, K. Wang, S. Li, X. Feng, C. Zhao and D. Feng, for additional assistance. Supported by the Ministry of Science and Technology of China (2013CB835300 and 2009CB522202), the National Natural Science Foundation of China (31170846), the open research fund of State Key Laboratory of Cellular Stress Biology at Xiamen University, and the US National Institutes of Health (CA035299).

Author information

Author notes

    • Xu-Dong Wang
    • , Yu Gong
    • , Zhi-Long Chen
    •  & Bei-Ni Gong

    These authors contributed equally to this work.

    • Amnon Altman
    •  & Yingqiu Li

    These authors jointly directed this work.

Affiliations

  1. State Key Laboratory of Biocontrol, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

    • Xu-Dong Wang
    • , Yu Gong
    • , Zhi-Long Chen
    • , Bei-Ni Gong
    • , Ji-Ji Xie
    • , Qi-Long Wang
    • , Liang-Hui Diao
    • , Anlong Xu
    •  & Yingqiu Li
  2. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.

    • Ji-Ji Xie
    •  & Amnon Altman
  3. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.

    • Chuan-Qi Zhong
    •  & Jiahuai Han

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Contributions

X.-D.W., Y.G., Z.-L.C. and B.-N.G. did experiments and analyzed data; X.-D.W. and Y.G. prepared materials; J.-J.X. did experiments with Prkcq−/− T cells; C.-Q.Z. performed MS experiments; Q.-L.W. helped with experiments with human primary T cells; L.-H.D. helped with experiments with confocal imaging; A.X. contributed reagents and suggestions; J.H. and A.A. contributed reagents, helped with some experimental design, analyzed data and edited the manuscript; and Y.L. conceived of and designed the experiments, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yingqiu Li.

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DOI

https://doi.org/10.1038/ni.3259

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