| First Author | Hu Z | Year | 2019 |
| Journal | Cell Metab | Volume | 30 |
| Issue | 2 | Pages | 290-302.e5 |
| PubMed ID | 31204281 | Mgi Jnum | J:282052 |
| Mgi Id | MGI:6355586 | Doi | 10.1016/j.cmet.2019.05.016 |
| Citation | Hu Z, et al. (2019) Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8(+) T Cells. Cell Metab 30(2):290-302.e5 |
| abstractText | CD8(+) T cell expansions and functions rely on glycolysis, but the mechanisms underlying CD8(+) T cell glycolytic metabolism remain elusive. Here, we show that acylglycerol kinase (AGK) is required for the establishment and maintenance of CD8(+) T cell metabolic and functional fitness. AGK deficiency dampens CD8(+) T cell antitumor functions in vivo and perturbs CD8(+) T cell proliferation in vitro. Activation of phosphatidylinositol-3-OH kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, which mediates elevated CD8(+) T cell glycolysis, is tightly dependent on AGK kinase activity. Mechanistically, T cell antigen receptor (TCR)- and CD28-stimulated recruitment of PTEN to the plasma membrane facilitates AGK-PTEN interaction and AGK-triggered PTEN phosphorylation, thereby restricting PTEN phosphatase activity in CD8(+) T cells. Collectively, these results demonstrate that AGK maintains CD8(+) T cell metabolic and functional state by restraining PTEN activity and highlight a critical role for AGK in CD8(+) T cell metabolic programming and effector function. |
