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Requirement of the expression of 3-phosphoglycerate dehydrogenase for traversing S phase in murine T lymphocytes following immobilized anti-CD3 activation.
Cellular Immunology ( IF 3.7 ) Pub Date : 2014-01-18 , DOI: 10.1016/j.cellimm.2013.12.003
Do Youn Jun 1 , Dennis Taub 2 , Francis J Chrest 2 , Young Ho Kim 1
Affiliation  

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.

中文翻译:


固定化抗 CD3 激活后,鼠 T 淋巴细胞中 3-磷酸甘油酸脱氢酶的表达需要穿越 S 期。



小鼠静息 (G(0)) T 淋巴细胞中未检测到催化 L-丝氨酸生物合成磷酸化途径第一步的 3-磷酸甘油酸脱氢酶 (PHGDH) mRNA。 G(0) T 细胞的固定化抗 CD3 激活在 G(1) 期表达 PHGDH mRNA,在 S 期达到最高水平。用固定化抗CD3加CsA或PBu(2)激活的G(0) T细胞不能驱动激活的T细胞进入S期,除非添加外源性rIL-2,否则不表达PHGDH mRNA。通过添加抗 IL-2 和抗 IL-2Rα 阻断 IL-2R 信号传导,导致 G(0) T 细胞的固定化抗 CD3 激活过程中 PHGDH mRNA 不表达。从培养基中去除L-丝氨酸或添加反义PHGDH寡核苷酸显着减少了活化T细胞的[(3)H]TdR掺入。这些结果表明,由 IL-2R 信号传导决定的 PHGDH 基因表达是激活 T 细胞 S 期 DNA 合成的关键事件。
更新日期:2013-12-18
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