Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation

Title
Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation
Author(s)
장재훈Shao-Cong Sun[Shao-Cong Sun]Mako Nakaya[Mako Nakaya]Yichuan Xiao[Yichuan Xiao]Xiaofei Zhou[Xiaofei Zhou]Mikyoung Chang[Mikyoung Chang]Xuhong Cheng[Xuhong Cheng]Marzenna Blonska[Marzenna Blonska]Xin Lin[Xin Lin]
Keywords
NF-KAPPA-B; MAMMALIAN TARGET; TRANSLATIONAL CONTROL; GLUCOSE-UPTAKE; C-MYC; DIFFERENTIATION; METABOLISM; RAPAMYCIN; EFFECTOR; PATHWAY
Issue Date
201405
Publisher
CELL PRESS
Citation
IMMUNITY, v.40, no.5, pp.692 - 705
Abstract
Glutamine has been implicated as an immunomodulatory nutrient, but how glutamine uptake is mediated during T cell activation is poorly understood. We have shown that naive T cell activation is coupled with rapid glutamine uptake, which depended on the amino acid transporter ASCT2. ASCT2 deficiency impaired the induction of T helper 1 (Th1) and Th17 cells and attenuated inflammatory T cell responses in mouse models of immunity and autoimmunity. Mechanistically, ASCT2 was required for T cell receptor (TCR)-stimulated activation of the metabolic kinase mTORC1. We have further shown that TCR-stimulated glutamine uptake and mTORC1 activation also required a TCR signaling complex composed of the scaffold protein CARMA1, the adaptor molecule BCL10, and the paracaspase MALT1. This function was independent of IKK kinase, a major downstream target of the CARMA1 complex. These findings highlight a mechanism of T cell activation involving ASCT2-dependent integration of the TCR signal and a metabolic signaling pathway.
URI
http://hdl.handle.net/YU.REPOSITORY/32332http://dx.doi.org/10.1016/j.immuni.2014.04.007
ISSN
1074-7613
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약학대학 > 약학부 > Articles
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