| First Author | Guittard G | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 5336 |
| PubMed ID | 29593227 | Mgi Jnum | J:323708 |
| Mgi Id | MGI:6851048 | Doi | 10.1038/s41598-018-23549-2 |
| Citation | Guittard G, et al. (2018) The Cish SH2 domain is essential for PLC-gamma1 regulation in TCR stimulated CD8(+) T cells. Sci Rep 8(1):5336 |
| abstractText | 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-gamma1 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-gamma1 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-gamma1 ubiquitination and degradation. This domain was essential for the Cish-mediated inhibition of Ca(2+) 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 an increased release of IFN-gamma and TNF-alpha. Using imaging we showed that Cish was expressed mostly in the cytoplasm and we did not see any Cish clustering at the plasma membrane upon stimulation. We conclude that the Cish-SH2 domain is essential for PLC-gamma1 regulation in TCR-stimulated CD8(+) T cells. |
