Rehfeld Jens F, Agersnap Mikkel
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
Regul Pept. 2012 Jan 10;173(1-3):1-5. doi: 10.1016/j.regpep.2011.09.009. Epub 2011 Oct 8.
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.
酪氨酰O-硫酸化是蛋白质常见的翻译后修饰，这种修饰也可能发生在调节肽上。其中包括胆囊收缩素（CCK）/胃泌素家族的成员。虽然胃泌素肽的硫酸化对其生物活性没有影响，但O-硫酸化对于CCK肽的胆囊收缩活性（即胆囊排空）至关重要。因此，最初是通过其胆囊排空效应来监测作为硫酸化肽的CCK的纯化过程。从那时起，CCK肽总是硫酸化的这一观点就一直存在。从语义角度来看，这个观点是正确的，因为胆囊只表达需要配体硫酸化的CCK-A受体。然而，CCK肽也是CCK-B受体的配体，而CCK-B受体不需要配体硫酸化。因此，未硫酸化的CCK肽可能通过CCK-B受体发挥作用。由于已经报道了体内存在具有完整α-酰胺化C末端四肽序列（-Trp-Met-Asp-PheNH₂）的proCCK未硫酸化产物，未硫酸化的CCK肽很可能构成一个通过CCK-B受体发挥作用的独立激素系统。这篇综述讨论了未硫酸化CCK肽的存在、分子形式以及可能的生理和病理生理意义。
