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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Butadienes / pharmacology
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CD28 Antigens / immunology
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CD3 Complex / immunology
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Cell Line, Tumor
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Cells, Cultured
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Enzyme Assays
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Enzyme Inhibitors / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Glucose / metabolism*
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Glucose / pharmacokinetics
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Glycolysis / drug effects
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Hexokinase / genetics
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Hexokinase / metabolism
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Imidazoles / pharmacology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / immunology*
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Mice
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Mice, Inbred C57BL
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Nitriles / pharmacology
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Pyridines / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antibodies, Monoclonal
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Butadienes
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CD28 Antigens
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CD3 Complex
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Enzyme Inhibitors
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Imidazoles
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Nitriles
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Pyridines
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U 0126
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Hexokinase
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Glucose
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SB 203580