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The cytosolic branched‐chain aminotransferase (BCATc) regulates T cell activation via mTOR signaling pathway
Author(s) -
Ananieva Elitsa A,
Patel Chirag,
Powell Jonathan,
Hutson Susan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.127.6
Subject(s) - pi3k/akt/mtor pathway , immune system , t cell , mechanistic target of rapamycin , microbiology and biotechnology , phosphorylation , biology , signal transduction , regulatory t cell , chemistry , il 2 receptor , immunology
The mammalian target of rapamycin (mTOR) integrates environmental cues such as amino acids and growth factors to direct T cell activation and differentiation. T cells have unique metabolic demands to support their own differentiation into subsets with specific functions to promote or suppress immunity. Here we describe a new candidate for an immunosupressive enzyme, the cytosolic branched‐chain aminotransferase (BCATc), which impacts mTOR signaling in T cells. BCATc is a metabolic enzyme that catalyzes the first step in leucine, isoleucine and valine degradation. BCATc protein levels and activity are 15‐ and 13‐fold higher under anergy, an immunological condition known as absence of an immune response. Under anergic conditions, T cells isolated from BCATc−/− mice had an up‐regulated mTOR signaling compared to anergic T cells isolated from wildtype mice. Phosphorylation of the mTOR substrates, S6 and 4EBP‐1, were 3.9 and 4.9 fold higher than in wildtype mice. The results suggest that BCATc or changes in BCAA metabolites may inhibit mTOR signaling under anergy and that lack of BCATc enzyme reverses the inhibition, possibly triggering T cells to full activation. Understanding the role of BCATc in T cell immunity will provide new strategies for nutritional therapy in modulating the immune response to promote treatment of autoimmune diseases or develop anti‐tumor vaccines. (Support: R01DK 34738 & Virginia Tech).