Abstract
Long-term survival of T lymphocytes in quiescent state is essential to maintain their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5) causes peripheral T lymphopenia due to spontaneous death of T cells. The underlying mechanism responsible for the disruption of quiescence in Gimap5 deficient T cells remains largely unknown. In this study, we show that loss of functional Gimap5 results in increased basal activation of mammalian target of rapamycin (mTOR), independent of protein phosphatase 2A (PP2A) or AMP-activated protein kinase (AMPK). Our results suggest that the constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway may be one of the consequences of the absence of functional GIMAP5.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Animals
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Blotting, Western
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Chromones
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Electrophoresis, Polyacrylamide Gel
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Female
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism*
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Male
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Mice
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Morpholines
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Oxygen Consumption / physiology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Protein Phosphatase 2 / genetics
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Protein Phosphatase 2 / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Rats
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
Substances
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Chromones
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Gimap5 protein, mouse
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinases
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Protein Phosphatase 2
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GTP Phosphohydrolases
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GTP-Binding Proteins
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Gimap5 protein, rat