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DAPK1 (death associated protein kinase 1) mediates mTORC1 activation and antiviral activities in CD8(+) T cells
- Source :
- Cell Mol Immunol
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group UK, 2019.
-
Abstract
- Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8(+) T-cell differentiation and function. Despite the links between PI3K-AKT and mTORC1 activation in CD8(+) T cells, the molecular mechanism underlying mTORC1 activation remains unclear. Here, we show that both the kinase activity and the death domain of DAPK1 are required for maximal mTOR activation and CD8(+) T-cell function. We found that TCR-induced activation of calcineurin activates DAPK1, which subsequently interacts with TSC2 via its death domain and phosphorylates TSC2 to mediate mTORC1 activation. Furthermore, both the kinase domain and death domain of DAPK1 are required for CD8(+) T-cell antiviral responses in an LCMV infection model. Together, our data reveal a novel mechanism of mTORC1 activation that mediates optimal CD8(+) T-cell function and antiviral activity.
- Subjects :
- 0301 basic medicine
Immunology
mTORC1
CD8-Positive T-Lymphocytes
Mechanistic Target of Rapamycin Complex 1
Lymphocyte Activation
Antiviral Agents
Article
03 medical and health sciences
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Immunology and Allergy
Cytotoxic T cell
Animals
Arenaviridae Infections
Lymphocytic choriomeningitis virus
Kinase activity
Phosphorylation
PI3K/AKT/mTOR pathway
Death domain
Mice, Knockout
Chemistry
TOR Serine-Threonine Kinases
Cell Differentiation
Cell biology
Mice, Inbred C57BL
Death-Associated Protein Kinases
030104 developmental biology
Infectious Diseases
Protein kinase domain
Death-Associated Protein Kinase 1
biological phenomena, cell phenomena, and immunity
030215 immunology
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Mol Immunol
- Accession number :
- edsair.doi.dedup.....55d16593d43fd84af6b81a279c241ab5