Yosten Gina L C, Liu Jun, Ji Hong, Sandberg Kathryn, Speth Robert, Samson Willis K
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.
Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA.
J Physiol. 2016 Mar 15;594(6):1601-5. doi: 10.1113/JP270567. Epub 2015 Oct 13.
AUG sequences and short open reading frames are commonly present in the 5'-leader sequence of G protein-coupled receptor mRNAs. The presence of these upstream AUG sequences has been demonstrated to inhibit downstream receptor translation efficiency and, most recently, receptor signal transduction. A seven amino acid peptide encoded by a short open reading frame in exon 2 of the angiotensin type 1a receptor has been shown to inhibit non-G protein-coupled signalling of angiotensin II, without altering the classical G protein-coupled pathway activated by the ligand. This finding may lead to the development of a new class of angiotensin receptor antagonists with activities biased for one, but not all, of the signalling cascades activated by angiotensin II, which could have therapeutic implications for the myriad hormones and neurotransmitters that signal through G protein-coupled receptors.
AUG序列和短开放阅读框通常存在于G蛋白偶联受体mRNA的5'-前导序列中。这些上游AUG序列的存在已被证明会抑制下游受体的翻译效率，并且最近还发现其会抑制受体信号转导。血管紧张素1a受体第2外显子中的一个短开放阅读框编码的七氨基酸肽已被证明可抑制血管紧张素II的非G蛋白偶联信号传导，而不会改变由配体激活的经典G蛋白偶联途径。这一发现可能会导致开发出一类新型的血管紧张素受体拮抗剂，其活性偏向于血管紧张素II激活的一种而非全部信号级联反应，这可能对通过G蛋白偶联受体发出信号的众多激素和神经递质具有治疗意义。
