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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.
Pubmed ID: 31204281
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This unknown targets
View all literature mentionsThis isotype control targets Unknown Specificity
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser235/236) (D57.2.2E) XP Rabbit mAb
View all literature mentionsThis polyclonal targets TIMM17B
View all literature mentionsThis monoclonal targets PTEN
View all literature mentionsThis monoclonal targets IFN gamma
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)
View all literature mentionsThis monoclonal targets Phospho-Akt (Thr308) (C31E5E) Rabbit mAb
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD62L (L-Selectin)
View all literature mentionsThis monoclonal targets PD-1 (CD279)
View all literature mentionsThis monoclonal targets Adenine Nucleotide Translocase 1 antibody [5F51BB5AG7]
View all literature mentionsThis polyclonal targets Phospho-FoxO1 (Ser256)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets alpha Tubulin (TU-02)
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets p70 S6 Kinase, phospho (Thr389)
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis polyclonal targets CALR
View all literature mentionsThis monoclonal targets PI3 Kinase p85
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis polyclonal targets TIM22
View all literature mentionsMus musculus with name B6.129S7-Rag1tm1Mom/J from IMSR.
View all literature mentionsCell line MC-38 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsMus musculus with name B6.Cg-Tg(Cd4-cre)1Cwi/BfluJ from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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