DAPK1 (death associated protein kinase 1) mediates mTORC1 activation and antiviral activities in CD8+ T cells.

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.

• Authors: Zhengping Wei, Pingfei Li, Ran He, Huicheng Liu, Na Liu, Yu Xia, Guoyu Bi, Qiuyang Du, Minghui Xia, Lei Pei, Jing Wang, Guihua Wang, Zhao-Hui Tang, Xiang Cheng, Huabin Li, Zhuoya Li, Lilin Ye, Arian Laurence, Youming Lu, Xiang-Ping Yang
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 18 Issue 1 Pg. 138-149 (01 2021) ISSN: 2042-0226 [Electronic] China
• PMID: 31541182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• mTOR protein, mouse
• Dapk1 protein, mouse
• Death-Associated Protein Kinases
• Mechanistic Target of Rapamycin Complex 1
• TOR Serine-Threonine Kinases

Topics

• Animals
• Antiviral Agents (pharmacology)
• Arenaviridae Infections (immunology, prevention & control, virology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Differentiation
• Death-Associated Protein Kinases (physiology)
• Lymphocyte Activation
• Lymphocytic choriomeningitis virus (drug effects)
• Mechanistic Target of Rapamycin Complex 1 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphorylation
• Signal Transduction
• TOR Serine-Threonine Kinases (genetics, metabolism)