Requirement of the expression of 3-phosphoglycerate dehydrogenase for traversing S phase in murine T lymphocytes following immobilized anti-CD3 activation

Abstract Murine resting (G 0 ) T lymphocytes contained no detectable mRNA of 3-phosphoglycerate dehydrogenase (PHGDH) catalyzing the first step in the phosphorylated pathway of l -serine biosynthesis. Immobilized anti-CD3 activation of G 0 T cells expressed the PHGDH mRNA in G 1 with a maximum level in S phase. G 0 T cells activated with either immobilized anti-CD3 plus CsA or PBu 2 , which failed to drive the activated T cells to enter S phase, did not express the PHGDH mRNA unless exogenous rIL-2 was added. Blocking of IL-2R signaling by adding anti-IL-2 and anti-IL-2Rα resulted in no expression of the PHGDH mRNA during immobilized anti-CD3 activation of G 0 T cells. Deprivation of l -serine from culture medium or addition of antisense PHGDH oligonucleotide significantly reduced [ 3 H]TdR incorporation of activated T cells. These results indicate that the PHGDH gene expression, dictated by IL-2R signaling, is a crucial event for DNA synthesis during S phase of activated T cells.