Induction of glucose metabolism in stimulated T lymphocytes is regulated by mitogen-activated protein kinase signaling

PLoS One. 2010 Nov 10;5(11):e15425. doi: 10.1371/journal.pone.0015425.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Butadienes / pharmacology
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Cells, Cultured
  • Enzyme Assays
  • Enzyme Inhibitors / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacokinetics
  • Glycolysis / drug effects
  • Hexokinase / genetics
  • Hexokinase / metabolism
  • Imidazoles / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nitriles / pharmacology
  • Pyridines / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antibodies, Monoclonal
  • Butadienes
  • CD28 Antigens
  • CD3 Complex
  • Enzyme Inhibitors
  • Imidazoles
  • Nitriles
  • Pyridines
  • U 0126
  • Hexokinase
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Glucose
  • SB 203580