Back to Search
Start Over
The Cish SH2 domain is essential for PLC-gamma 1 regulation in TCR stimulated CD8(+) T cells
- Source :
- Scientific Reports, Scientific Reports, Nature Publishing Group, 2018, 8 (5336), ⟨10.1038/s41598-018-23549-2⟩, Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018), Scientific Reports, 2018, 8 (5336), ⟨10.1038/s41598-018-23549-2⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
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 an increased release of IFN-γ and TNF-α. 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-γ1 regulation in TCR-stimulated CD8+ T cells.
- Subjects :
- 0301 basic medicine
T cell
[SDV]Life Sciences [q-bio]
Receptors, Antigen, T-Cell
Gene Expression
lcsh:Medicine
Suppressor of Cytokine Signaling Proteins
Cytotoxic T cells
CD8-Positive T-Lymphocytes
Signal transduction
Lymphocyte Activation
SH2 domain
Article
Cell Line
src Homology Domains
Mice
03 medical and health sciences
medicine
Animals
Humans
Cytotoxic T cell
Protein Interaction Domains and Motifs
lcsh:Science
CISH
Mice, Knockout
Multidisciplinary
biology
Phospholipase C gamma
Chemistry
lcsh:R
T-cell receptor
3. Good health
Ubiquitin ligase
Cell biology
[SDV] Life Sciences [q-bio]
030104 developmental biology
medicine.anatomical_structure
biology.protein
Cytokines
Calcium
lcsh:Q
CD8
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Scientific Reports, Nature Publishing Group, 2018, 8 (5336), ⟨10.1038/s41598-018-23549-2⟩, Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018), Scientific Reports, 2018, 8 (5336), ⟨10.1038/s41598-018-23549-2⟩
- Accession number :
- edsair.doi.dedup.....9a7ad3d3ebf592eb8668b0b796bd265c
- Full Text :
- https://doi.org/10.1038/s41598-018-23549-2⟩