Kavanaugh W M, Harsh G R, Starksen N F, Rocco C M, Williams L T
Howard Hughes Medical Institute, University of California, San Francisco 94143.
J Biol Chem. 1988 Jun 15;263(17):8470-2.
Platelet-derived growth factor is expressed as dimers of two homologous polypeptide chains, termed A and B, encoded by different genes. A and B chain mRNA levels in microvascular endothelial cells are increased by phorbol ester, thrombin, and transforming growth factor-beta (TGF-beta) and are reduced by agents that elevate cyclic AMP. In this report, we investigated the effects of these regulatory agents on A and B chain transcription rates. By nuclear run-on analysis, TGF-beta stimulated transcription of both A and B chain genes. Thrombin and phorbol ester stimulated B chain transcription and had little or no detectable effect on A chain transcription. Pretreatment of cultures with 50 microM forskolin, a potent activator of adenylyl cyclase, completely blocked B chain transcription by thrombin and TGF-beta, but did not inhibit A chain transcription induced by TGF-beta. These results show that expression of platelet-derived growth factor mRNA involves both positive and negative transcriptional regulation and that there are differences in the transcriptional control of the A and B chain genes.
血小板衍生生长因子以由不同基因编码的两种同源多肽链（称为A链和B链）的二聚体形式表达。微血管内皮细胞中A链和B链的mRNA水平会因佛波酯、凝血酶和转化生长因子-β（TGF-β）而升高，并因能提高环磷酸腺苷水平的试剂而降低。在本报告中，我们研究了这些调节因子对A链和B链转录速率的影响。通过核转录分析，TGF-β刺激了A链和B链基因的转录。凝血酶和佛波酯刺激了B链转录，而对A链转录几乎没有或没有可检测到的影响。用50微摩尔的福斯可林（一种有效的腺苷酸环化酶激活剂）预处理培养物，可完全阻断凝血酶和TGF-β对B链的转录，但不抑制TGF-β诱导的A链转录。这些结果表明，血小板衍生生长因子mRNA的表达涉及正性和负性转录调控，并且A链和B链基因的转录控制存在差异。
