title: Unsulfated cholecystokinin: An overlooked hormone?
abstract: Tyrosyl O-sulfation is a common posttranslational derivatization of proteins that may also modify regulatory peptides. Among these are members of the cholecystokinin (CCK)/gastrin family. While sulfation of gastrin peptides is without effect on the bioactivity, O-sulfation is crucial for the cholecystokinetic activity (i.e. gallbladder emptying) of CCK peptides. Accordingly, the purification of CCK as a sulfated peptide was originally monitored by its gallbladder emptying effect. Since then, the dogma has prevailed that CCK peptides are always sulfated. The dogma is correct in a semantic context since the gallbladder expresses only the CCK-A receptor that requires sulfation of the ligand. CCK peptides, however, are also ligands for the CCK-B receptors that do not require ligand sulfation. Consequently, unsulfated CCK peptides may act via CCK-B receptors. Since in vivo occurrence of unsulfated products of proCCK with an intact α-amidated C-terminal tetrapeptide sequence (-Trp-Met-Asp-PheNH(2)) has been reported, it is likely that unsulfated CCK peptides constitute a separate hormone system that acts via CCK-B receptors. This review discusses the occurrence, molecular forms, and possible physiological as well as pathophysiological significance of unsulfated CCK peptides.
authors: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark. jens.f.rehfeld@rh.regionh.dk
authors: Jens F
authors: JF
authors: Rehfeld
authors: Mikkel
authors: M
authors: Agersnap
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D011949:Receptors, Cholecystokinin; C005662:tyrosine O-sulfate; D014443:Tyrosine; D002766:Cholecystokinin