title: The role and regulation of mTOR in T-lymphocyte function.
abstract: The conversion of naïve T cells into effector T cells is initiated by stimulation through the T-cell receptor (TCR). Upon activation, T cells undergo significant morphological and functional changes, putting new metabolic demands on the cell. Past research has identified the mammalian target of rapamycin (mTOR) as a critical regulator of cell metabolism, and the development of new genetic models has begun to reveal an important role for this pathway in the homeostasis and function of T lymphocytes. In this review, we focus on the most recent findings that demonstrate the ability of mTOR to regulate T-cell activation, CD8(+) memory cell formation and function, and helper T lineage differentiation. Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling.
authors.affiliation: Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: O'Brien
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000276:immunology / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C491790:RASGRP1 protein, human; D011948:Receptors, Antigen, T-Cell; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D019852:Diacylglycerol Kinase; D058570:TOR Serine-Threonine Kinases