Chambard J C, Pouysségur J
Centre de Biochimie, CNRS, Université de Nice, Faculté des Sciences, Parc Valrose, France.
J Cell Physiol. 1988 Apr;135(1):101-7. doi: 10.1002/jcp.1041350114.
Transforming growth factor beta (TGF-beta) was found to inhibit (IC50 = 0.1 ng/ml) alpha-thrombin or FGF-induced mitogenicity in G0-arrested Chinese hamster lung fibroblasts. Growth factor-stimulated cells became rapidly insensitive to TGF-beta addition during their progression through G0/G1 suggesting that an early step of the mitogenic response was the target of TGF-beta action. Surprisingly, none of the well characterized early mitogenic events commonly triggered by growth factors was found to be affected by TGF-beta addition. These responses included: phosphoinositide breakdown, activation of protein kinase C as determined by EGF receptor down-modulation, subsequent rises in pHi, c-fos, and c-myc mRNA levels, ribosomal protein S6 phosphorylation, the increase in RNA and protein synthesis, induction of ornithine decarboxylase. Only the induction of thymidine kinase, a marker of entry in the S phase, was found to be repressed by TGF-beta, with maximal inhibition when TGF-beta was added early in G1. These results indicate that the inhibitory action of TGF-beta does not affect the growth factors signalling pathways but touches an early event different from those so far analyzed.
转化生长因子β（TGF-β）被发现可抑制（IC50 = 0.1 ng/ml）α-凝血酶或成纤维细胞生长因子（FGF）诱导的处于G0期停滞的中国仓鼠肺成纤维细胞的有丝分裂活性。在生长因子刺激的细胞通过G0/G1期的过程中，它们会迅速对添加的TGF-β变得不敏感，这表明有丝分裂反应的早期步骤是TGF-β作用的靶点。令人惊讶的是，未发现生长因子通常触发的任何特征明确的早期有丝分裂事件会受到添加TGF-β的影响。这些反应包括：磷酸肌醇分解、通过表皮生长因子（EGF）受体下调测定的蛋白激酶C激活、随后细胞内pH值升高、c-fos和c-myc mRNA水平升高、核糖体蛋白S6磷酸化、RNA和蛋白质合成增加、鸟氨酸脱羧酶诱导。仅胸苷激酶的诱导（S期进入的标志物）被发现受到TGF-β的抑制，在G1期早期添加TGF-β时抑制作用最大。这些结果表明，TGF-β的抑制作用并不影响生长因子信号通路，而是涉及一个与迄今为止分析的事件不同的早期事件。
