Two alternative processing pathways for a preprohormone: a bioactive form of secretin.
An N-terminally 9-residue elongated form of secretin, secretin-(-9 to 27) amide, was isolated from porcine intestinal tissue and characterized. Current knowledge about peptide processing sites does not allow unambiguous prediction of the signal peptide cleavage site in preprosecretin but suggests cleavage in the region of residues -10 to -14 counted upstream from the N terminus of the hormone. However, the structure of the isolated peptide suggests that the cleavage between the signal peptide and the N-terminal propeptide occurs at the C-terminal side of residue -10. Moreover, the isolated peptide demonstrates that secretin can be fully processed C-terminally prior to the final N-terminal cleavage. The results from this report, and those from earlier studies, where C-terminally elongated variants were isolated, show that the processing of the secretin precursor may proceed by one of two alternative pathways, in which either of the two ends is processed first. The bioactivity of the N-terminally extended peptide on exocrine pancreatic secretion was lower than that of secretin, indicating the importance of the finally processed free N terminus of the hormone for interaction with secretin receptors.
Bonetto
V
V
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Jörnvall
H
H
Mutt
V
V
Sillard
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism; D051381:Rats; D012633:Secretin / Q000096:biosynthesis* / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013552:Swine
D011498:Protein Precursors; D021382:Protein Sorting Signals; C065605:prosecretin; D012633:Secretin