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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CD28 Antigens / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Filamins / metabolism
  • HEK293 Cells
  • Humans
  • Immunological Synapses / metabolism
  • Isoenzymes / chemistry
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation
  • Lysine / chemistry
  • Mice
  • Mice, Knockout
  • Mutagenesis, Site-Directed
  • Protein Inhibitors of Activated STAT / metabolism
  • Protein Kinase C / chemistry
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • Sumoylation
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / enzymology
  • Th2 Cells / immunology


  • CD28 Antigens
  • Filamins
  • Isoenzymes
  • PIAS2 protein, human
  • Protein Inhibitors of Activated STAT
  • Receptors, Antigen, T-Cell
  • PRKCQ protein, human
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Lysine