Abstract
The orexigenic hormone ghrelin is a 28-amino-acid peptide derived from a 99-amino-acid precursor and acylated at Ser-3, which was initially isolated from rat stomach. In addition to stimulating appetite and growth, it also plays various important roles in energy homeostasis and in the cardiovascular and immune systems. Although analysis of its physiological effects has yielded many significant results, much less information is available on its biosynthesis and the mechanism of its acylation. In this report, we have studied the endoproteolytic processing of this molecule from its precursor (proghrelin) into mature ghrelin in various prohormone convertase null mouse strains generated in our laboratory and have identified the convertase responsible for this event. Using Western blotting, mass spectrometry, and immunocytochemical methods, we have demonstrated that (a) in mouse stomach, prohormone convertase 1/3 (PC1/3) is the endoprotease responsible for the conversion of proghrelin to ghrelin, (b) the acylation of this peptide is processing-independent, and (c) the expression of proghrelin mRNA is increased in the processing-deficient (PC1/3 null) mouse.
Highlights
Similar to many other peptide hormones, ghrelin is processed from a 94-amino-acid precursor
It is well established that many bioactive peptide hormones are generated by limited proteolytic processing by members of a secretory pathway-specialized serine protease family related to yeast Kex2, which includes prohormone convertase 1/3 (PC1/3), PC2, and PC5/6A [19, 20]
PC1/3 is involved in this process, we analyzed ghrelin processing in PC1/3 null mouse stomachs
Summary
The orexigenic hormone ghrelin is a 28-amino-acid peptide derived from a 99-amino-acid precursor and acylated at Ser-3, which was initially isolated from rat stomach. A 28-amino-acid peptide, was initially isolated from rat stomach [1] as a ligand of the growth hormone secretagogue receptor [2]. Subsequent studies have revealed that it is a potent orexigenic peptide [3] It is involved in various functions of the heart [4], pancreatic islets, and insulin secretion [5,6,7,8,9,10] and in insulin signaling [11], adipose tissue [12], and the immune system [13]. We investigate the processing of proghrelin in various prohormone convertase-deficient mouse models available in our laboratory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
