PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells
DK Finlay, E Rosenzweig, LV Sinclair… - Journal of Experimental …, 2012 - rupress.org
DK Finlay, E Rosenzweig, LV Sinclair, C Feijoo-Carnero, JL Hukelmann, J Rolf…
Journal of Experimental Medicine, 2012•rupress.orgRESULTS mTORC1 regulates glucose uptake and glycolysis in TCR-and IL-2–stimulated
CD8+ T cells TCR triggering of naive CD8+ T cells with peptide–MHC complexes induced
expression of the glucose transporter Glut1 and a concomitant increase in glucose uptake
and lactate output (Fig. 1, A–C). TCR triggering also activated mTORC1 activity (Fig. 1 D), as
judged by assessing the impact of TCR ligation on phosphorylation of mTORC1 substrate
sequences on S6K1 (T389 and S421/424) and the phosphorylation of the S6K1 substrate …
CD8+ T cells TCR triggering of naive CD8+ T cells with peptide–MHC complexes induced
expression of the glucose transporter Glut1 and a concomitant increase in glucose uptake
and lactate output (Fig. 1, A–C). TCR triggering also activated mTORC1 activity (Fig. 1 D), as
judged by assessing the impact of TCR ligation on phosphorylation of mTORC1 substrate
sequences on S6K1 (T389 and S421/424) and the phosphorylation of the S6K1 substrate …
RESULTS mTORC1 regulates glucose uptake and glycolysis in TCR-and IL-2–stimulated CD8+ T cells
TCR triggering of naive CD8+ T cells with peptide–MHC complexes induced expression of the glucose transporter Glut1 and a concomitant increase in glucose uptake and lactate output (Fig. 1, A–C). TCR triggering also activated mTORC1 activity (Fig. 1 D), as judged by assessing the impact of TCR ligation on phosphorylation of mTORC1 substrate sequences on S6K1 (T389 and S421/424) and the phosphorylation of the S6K1 substrate S6 ribosomal protein (S235/236). The inhibition of mTORC1 activity with rapamycin blocked TCR-induced increases in Glut1 expression and glucose uptake and reduced lactate production (Fig. 1, E–G). TCR-primed CD8+
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