title: GIMAP5 Deficiency Is Associated with Increased AKT Activity in T Lymphocytes.
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.
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Marian
authors.initials: M
authors.lastname: Mayhue
authors.affiliation: Department of Pediatrics, Division of Cellular and Molecular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States of America.
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada; Centre de Recherche Clinique, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada; Centre de Recherche Clinique, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002867:Chromones; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009025:Morpholines; D010101:Oxygen Consumption / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D002867:Chromones; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054648:Protein Phosphatase 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C534135:Gimap5 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494977:Gimap5 protein, rat