A 5'-upstream short open reading frame encoded peptide regulates angiotensin type 1a receptor production and signalling via the β-arrestin pathway.
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.
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.
Gina L C
GL
Yosten
Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Jun
J
Liu
Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Hong
H
Ji
Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Kathryn
K
Sandberg
Department of Pharmaceutical Sciences, Nova University, Fort Lauderdale, FL, USA.
Robert
R
Speth
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.
Willis K
WK
Samson
D020121:5' Untranslated Regions; D000818:Animals; D006801:Humans; D016366:Open Reading Frames; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071557:beta-Arrestins / Q000378:metabolism*
D020121:5' Untranslated Regions; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D000071557:beta-Arrestins