Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression.
Distinct pathways regulate transforming growth factor beta 1-stimulated proto-oncogene and extracellular matrix gene expression.
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不同的途径调节转化生长因子β1刺激的原癌基因和细胞外基质基因的表达。
DOI：
10.1002/jcp.1041420106
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发表时间：
1990
影响因子：
5.6
通讯作者：
Leof,EB
中科院分区：
文献类型：
--
作者：
Howe,PH;Cunningham,MR;Leof,EB
在AKR‐2B成纤维细胞中研究了百日咳毒素（PT）对转化生长因子β1 （tgf - β1）诱导的原癌基因表达的影响。tgf - β 1刺激后，PT实质上消除了c - sis和c - myc mRNA的表达。这种抑制作用对tgf - β1刺激的原癌基因表达是特异性的，并且与41 - kDa底物的ADP -核糖基化有关。放线菌素D衰变和核运行实验表明，PT的抑制作用是转录激活减少的结果，而不是原癌基因信息衰变增加的结果。然而，PT不影响tgf β 1刺激的纤维连接蛋白和胶原mRNA的积累，也没有对tgf β 1诱导的形态转化产生任何抑制作用。这些数据表明，tgf - β 1刺激的基因表达与多种通路相耦合，这些通路对PT敏感。
The effect of pertussis toxin (PT) on transforming growth factor β1 (TGFβl)‐induced proto‐oncogene expression was investigated in AKR‐2B fibroblasts. PT substantially abolished c‐sis and c‐myc mRNA expression following TGFβl stimulation. This inhibitory effect was specific for TGFβ1‐stimulated proto‐oncogene expression and associated with the ADP‐ribosylation of a 41‐kDa substrate. Actinomycin D decay and nuclear run‐on experiments demonstrated that the inhibitory effects of PT are a result of decreased transcriptional activation and not to an increased decay of proto‐oncogene message. PT did not, however, affect TGFβl‐stimulated fibronectin and collagen mRNA accumulation nor did it have any inhibitory effect on TGFβl‐induced morphological transformation. These data indicate that TGFβl‐stimulated gene expression is coupled to multiple pathways distinguished by their sensitivity to PT.