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Nat Immunol. 2015 Nov;16(11):1195-203. doi: 10.1038/ni.3259. Epub 2015 Sep 21.

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

Author information

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.
2
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
3
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.

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.

PMID:
26390157
DOI:
10.1038/ni.3259
[Indexed for MEDLINE]

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