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

Xu-Dong Wang1, Yu Gong1, Zhi-Long Chen1

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

Nature Immunology
|September 22, 2015
PubMed

Insights

Sumoylation of protein kinase C-theta (PKC-θ) is crucial for T cell activation. This process regulates the formation of the immunological synapse and T cell receptor signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Sumoylation is a post-translational modification regulating diverse cellular processes.
  • The role of sumoylation in T cell receptor (TCR) signaling pathways was previously uncharacterized.

Purpose of the Study:

  • To investigate the role of sumoylation in T cell activation and TCR signaling.
  • To identify the specific sumoylation events and regulators involved in PKC-θ function.

Main Methods:

  • Utilized primary mouse and human T cells.
  • Investigated protein sumoylation using biochemical assays.
  • Analyzed protein-protein interactions and immunological synapse formation.

Main Results:

  • Protein kinase C-theta (PKC-θ) undergoes sumoylation upon TCR and CD28 costimulation at Lys325 and Lys506.
  • PIASxβ was identified as the SUMO E3 ligase for PKC-θ.
  • Sumoylation of PKC-θ is essential for T cell activation, immunological synapse maturation, and co-accumulation of PKC-θ and CD28.

Conclusions:

  • Sumoylation is a critical regulator of TCR-proximal signaling.
  • Sumoylation of PKC-θ is indispensable for the formation of a mature immunological synapse and effective T cell activation.

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