T lymphocytes play a critical role in a cell-mediated immune response. During activation, extracellular and intracellular signals alter T cell metabolism in order to meet the energetic and biometabolic needs of a proliferating, active cell, but control of these phenomena is not well defined. The idea that metabolism can be regulated directly via receptor-mediated signals is being investigated. The T cell receptor (TCR) and CD28 pathways were stimulated and signaling was modified using chemical inhibitors of MAP kinases. Metabolic changes were monitored using assays for glucose uptake, hexokinase activity, glycolysis, Krebs Cycle, and pentose phosphate pathway. Two MAPK pathways (ERK, JNK) appear to be determining factors because their inhibition downregulated metabolism. Inhibition of another MAPK pathway (p38) causes some downregulation of these activities but the effect is not as strong as with the ERK and JNK inhibitors, suggesting that the p38 pathway is less important in regulating glucose metabolism.
|Advisor:||Frauwirth, Kenneth A.|
|Commitee:||Mosser, David M., Stewart, Richard C., Wu, Louisa P.|
|School:||University of Maryland, College Park|
|Department:||Cell Biology & Molecular Genetics|
|School Location:||United States -- Maryland|
|Source:||MAI 49/04M, Masters Abstracts International|
|Subjects:||Molecular biology, Cellular biology, Immunology|
|Keywords:||Glucose uptake, Glycolysis, Krebs cycle and pentose phosphate pathway, MAPK signal, T cell, Transcription factor|
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