The CD28 signaling pathway regulates glucose metabolism.
Lymphocyte activation initiates a program of cell growth, proliferation, and differentiation that increases metabolic demand. Although T cells increase glucose uptake and glycolysis during an immune response, the signaling pathways that regulate these increases remain largely unknown. Here we show that CD28 costimulation, acting through phosphatidylinositol 3'-kinase (PI3K) and Akt, is required for T cells to increase their glycolytic rate in response to activation. Furthermore, CD28 controls a primary response pathway, inducing a level of glucose uptake and glycolysis in excess of that needed to maintain cellular ATP/ADP levels or macromolecular synthesis. These data suggest that CD28 costimulation functions to increase glycolytic flux, allowing T cells to anticipate energetic and biosynthetic needs associated with a sustained response.
Frauwirth
Kenneth A
KA
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Riley
James L
JL
Harris
Marian H
MH
Parry
Richard V
RV
Rathmell
Jeffrey C
JC
Plas
David R
DR
Elstrom
Rebecca L
RL
June
Carl H
CH
Thompson
Craig B
CB
D000244:Adenosine Diphosphate / Q000378:metabolism; D001665:Binding Sites; D018106:CD28 Antigens / Q000502:physiology*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence
D000244:Adenosine Diphosphate; D018106:CD28 Antigens; D005947:Glucose; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C495677:SLC2A1 protein, human; C494918:AKT1 protein, human