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

• PHGDH gene expression was dictated by IL-2R signaling in activated T cells.
• l-Serine deprivation from culture medium suppressed [3H]TdR incorporation of T cells.
• Antisense PHGDH oligonucleotide effectively reduced [3H]TdR incorporation of T cells.
• PHGDH gene expression is required for traversing S phase in activated T cells.

Murine resting (G0) 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 G0 T cells expressed the PHGDH mRNA in G1 with a maximum level in S phase. G0 T cells activated with either immobilized anti-CD3 plus CsA or PBu2, 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 G0 T cells. Deprivation of l-serine from culture medium or addition of antisense PHGDH oligonucleotide significantly reduced [3H]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.