title: Induction of glucose metabolism in stimulated T lymphocytes is regulated by mitogen-activated protein kinase signaling.
abstract: T lymphocytes play a critical role in cell-mediated immune responses. During activation, extracellular and intracellular signals alter T cell metabolism in order to meet the energetic and biosynthetic needs of a proliferating, active cell, but control of these phenomena is not well defined. Previous studies have demonstrated that signaling from the costimulatory receptor CD28 enhances glucose utilization via the phosphatidylinositol-3-kinase (PI3K) pathway. However, since CD28 ligation alone does not induce glucose metabolism in resting T cells, contributions from T cell receptor-initiated signaling pathways must also be important. We therefore investigated the role of mitogen-activated protein kinase (MAPK) signaling in the regulation of mouse T cell glucose metabolism. T cell stimulation strongly induces glucose uptake and glycolysis, both of which are severely impaired by inhibition of extracellular signal-regulated kinase (ERK), whereas p38 inhibition had a much smaller effect. Activation also induced hexokinase activity and expression in T cells, and both were similarly dependent on ERK signaling. Thus, the ERK signaling pathway cooperates with PI3K to induce glucose utilization in activated T cells, with hexokinase serving as a potential point for coordinated regulation.
authors.affiliation: Department of Cell Biology and Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Aimee J
authors.initials: AJ
authors.lastname: Marko
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Miller
authors.forename: Alina
authors.initials: A
authors.lastname: Kelman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Frauwirth
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002070:Butadienes; D018106:CD28 Antigens; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; D006593:Hexokinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580