The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8⁺ T cells.

ABSTRACT: Cish, participates within a multi-molecular E3 ubiquitin ligase complex, which ubiquitinates target proteins. It has an inhibitory effect on T cell activation mediated by PLC-γ1 regulation, and it functions as a potent checkpoint in CD8⁺ T cell tumor immunotherapy. To study the structural and functional relationships between Cish and PLC-γ1 during CD8⁺ T cell activation, we tested mutants of the Cish-SH2 (R107K) and D/BC (L222Q, C226Q) domains. We confirmed that Cish-SH2-specific binding was essential for PLC-γ1 ubiquitination and degradation. This domain was essential for the Cish-mediated inhibition of Ca²⁺ release upon TCR stimulation. No effect on inhibition of cytokine release was observed with SH2 or D/BC mutants, although the absence of Cish led to a

SUBMITTER: Guittard G 

PROVIDER: S-EPMC5871872 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature