title: 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.
authors.affiliation: Laboratory of Immunobiology, School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Do Youn
authors.initials: do Y
authors.lastname: Jun
authors.affiliation: Laboratory of Immunology, Gerontology Research Center, NIA, NIH, Baltimore, MD 21224, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Taub
authors.affiliation: Laboratory of Immunology, Gerontology Research Center, NIA, NIH, Baltimore, MD 21224, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Chrest
authors.affiliation: Laboratory of Immunobiology, School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: ykim@knu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000201:enzymology / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D012694:Serine / Q000172:deficiency; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D017252:CD3 Complex; D015375:Receptors, Interleukin-2; D012694:Serine; D050543:Phosphoglycerate Dehydrogenase
keywords: Antisense oligonucleotide; IL-2R signaling; PHGDH; S phase; T cell activation; The phosphorylated pathway; l-Serine biosynthesis