Sci. STKE, 2 July 2002
Metabolism Ensuring Sufficient Energy Supply
T cells lack glycogen stores to draw upon when stimulated. And stimulated T cells have a much higher energy demand than resting T cells: they double in size, convert to a proliferative phenotype, and convert to an actively secretory phenotype. Frauwirth et al. provide evidence that costimulation of the T cell receptor complex by CD28, which stimulates a prolonged activation of the serine-threonine kinase Akt that is downstream of phosphatidylinositol 3-kinase (PI3K), directly stimulates glucose uptake and glycolysis. CD28 costimulation stimulated the expression of the Glut1 glucose uptake transporter, stimulated glucose uptake, and stimulated glycolysis with a concomitant secretion of lactate. Thus, the stimulated T cells adjust glucose availability and metabolism in response to receptor and coreceptor stimulation, instead of in response to depletion of cellular energy stores. The secretion of lactate is interpreted to mean that the cells are not responding to a drop in cellular adenosine triphosphate concentration, but are increasing glycolytic flux in excess of the cellular metabolic requirements. Thus, through a mechanism analagous to that initiated by insulin, CD28 costimulation enhances glucose availability and metabolism through activation of the PI3K-Akt pathway, allowing the cells to meet, indeed even exceed, their metabolic requirements through increased glycolytic flux.
K. A. Frauwirth, J. L. Riley, M. H. Harris, R. V. Parry, J. C. Rathmell, D. R. Plas, R. L. Elstrom, C. H. Jume, C. B. Thompson, The CD28 signaling pathway regulates glucose metabolism. Immunity 16, 769-777 (2002). [Online Journal]
Citation: Ensuring Sufficient Energy Supply. Sci. STKE 2002, tw229 (2002).
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