Reconstitution of angiotensin receptor mRNA down-regulation in vascular smooth muscle. Post-transcriptional control by protein kinase a but not mitogenic signaling directed by the 5'-untranslated region.
Reconstitution of angiotensin receptor mRNA down-regulation in vascular smooth muscle. Post-transcriptional control by protein kinase a but not mitogenic signaling directed by the 5'-untranslated region.
复制标题
血管平滑肌中血管紧张素受体 mRNA 下调的重建。
DOI：
10.1074/jbc.275.11.7604
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Murphy,TJ
中科院分区：
文献类型：
--
作者：
Xu,K;Murphy,TJ
Cell surface receptor activation generally leads to changes in mRNA abundance, which may involve regulatory targets in processes working at the post-transcriptional level. Many types of agonists down-regulate vascular smooth muscle angiotensin receptor (AT1-R) gene expression, but it is unclear which of these activate post-transcriptional mechanisms. To reconstitute faithfully the normal AT1-R mRNA regulatory environment, tetracycline-suppressible promoters drive highly accurate recombinant AT1-R mRNA mimics in vascular smooth muscle cells that co-express an endogenous AT1-R mRNA. Down-regulation of the latter occurs shortly after stimulating mitogenic receptors or by using forskolin, but only cAMP signaling reduces expression of the recombinant AT1-R mRNA. Transcription of the recombinant mRNA is unaffected by cAMP signaling. Deletions of the AT1-R mRNA 3′-untranslated region do not impair cAMP-mediated down-regulation. Both loss of function and gain of function mutants show the response is mediated by the 5′-untranslated region. These observations provide the first direct functional evidence for modulation of vascular AT1-R gene expression by a mechanism involving a protein kinase A-regulated post-transcriptional process.
