T Cell Receptor (TCR)-Induced PLC-?1 Sumoylation via PIASx? and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-?1.

ABSTRACT: The SUMO modification system plays an important role in T cell activation, yet how sumoylation regulates TCR-proximal signaling remains largely unknown. We show here that Phospholipase C-?1 (PLC-?1) is conjugated by SUMO1 at K54 and K987 upon TCR stimulation and that K54 sumoylation is pivotal for PLC-?1-mediated T cell activation. We further demonstrate that TCR-induced K54 sumoylation of PLC-?1 significantly promotes the formation of PLC-?1 microclusters and the association of PLC-?1 with the adaptor proteins SLP76 and Gads, but only slightly affects the phosphorylation of PLC-?1 on Y783, which determines the enzyme catalytic activity. Moreover, upon TCR stimulation, the SUMO E3 ligases PIASx? and PIAS3 both interact with PLC-?1 and cooperate to sumoylate PLC-?1, facilitating the assembly of PLC-?1 microclusters. Together, our findings reveal a critical role of PLC-?1 K54 sumoylation in PLC-?1 microcluster assembly that controls PLC-?1-mediated T cell activation, suggesting that sumoylation may have an important role in the microcluster assembly of TCR-proximal signaling proteins.

SUBMITTER: Wang QL 

PROVIDER: S-EPMC6403162 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature