Van Obberghen-Schilling E, Chambard J C, Paris S, L'Allemain G, Pouysségur J
EMBO J. 1985 Nov;4(11):2927-32. doi: 10.1002/j.1460-2075.1985.tb04025.x.
In resting Chinese hamster fibroblasts (CCL39) alpha-thrombin rapidly stimulates several biochemical events implicated in the mitogenic response, including the breakdown of inositol phospholipids, activation of a plasma membrane Na+/H+ antiporter, phosphorylation of ribosomal protein S6 and increased expression of the proto-oncogene c-myc. Complete removal of the growth factor during cellular G0/G1 transit precludes the re-initiation of DNA synthesis. The present study was designed to examine the fate of alpha-thrombin-activated early events following growth factor inactivation. In cells stimulated for 30 min with alpha-thrombin, neutralization of the growth factor results in: (i) immediate arrest of inositol phosphate formation, (ii) rapid inactivation of Na+/H+ exchange, (iii) deactivation of the S6 phosphorylating system and (iv) strong reduction of c-myc mRNA level. Our findings that commitment for DNA synthesis as well as persistent activation of 'early' cellular events requires continual growth factor stimulation suggest that: (i) growth factor-induced transmembrane signals have a short life and (ii) the generation of these signals during the 8 h of the pre-replicative phase is required for G0-arrested cells to enter the S phase.
在静止的中国仓鼠成纤维细胞（CCL39）中，α-凝血酶能迅速刺激几种与有丝分裂反应相关的生化事件，包括肌醇磷脂的分解、质膜Na⁺/H⁺反向转运体的激活、核糖体蛋白S6的磷酸化以及原癌基因c-myc表达的增加。在细胞G0/G1期转变过程中完全去除生长因子会阻止DNA合成的重新启动。本研究旨在探讨生长因子失活后α-凝血酶激活的早期事件的命运。在用α-凝血酶刺激30分钟的细胞中，生长因子的中和导致：（i）肌醇磷酸形成立即停止，（ii）Na⁺/H⁺交换迅速失活，（iii）S6磷酸化系统失活，以及（iv）c-myc mRNA水平大幅降低。我们的研究结果表明，DNA合成的启动以及“早期”细胞事件的持续激活需要持续的生长因子刺激，这表明：（i）生长因子诱导的跨膜信号寿命较短，（ii）G0期停滞的细胞进入S期需要在复制前阶段的8小时内产生这些信号。
