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

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-theta 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 PIASx beta as a ligase for PKC-theta. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-theta was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-theta but inhibited the association of CD28 with PKC-theta and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-theta and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-theta is essential for the formation of a mature immunological synapse and T cell activation.