Unique progastrin processing in equine G-cells suggests marginal tyrosyl sulfotransferase activity.
Previous studies have indicated that equine G-cell processing of progastrin differs from that of other species. Since the difference may be due to structural features, we have identified equine gastrin-17 and -34 (<ELGLQGSPHLVADLSKKQGPWLEKEEAAYGWMDF-NH2), and cloned a corresponding 451-bp cDNA that encodes a 107-amino-acid preprogastrin. Comparison with other mammalian gastrins shows a high degree of conservation, but instead of four or five acidic residues preceding the bioactive carboxyamidated C-terminal heptapeptide, equine gastrin contains the remarkable substitution of Lys for Glu in this presumed invariant region. In contrast with known mammalian gastrins, which are all significantly Tyr-sulphated, the equine antral gastrins are virtually non-sulphated. Transfection of the equine preprogastrin cDNA into an endocrine cell line resulted in highly sulphated gastrins, indicating that the absence of in situ sulphation is not due to the structure of gastrin, but occurs rather because the equine antral G-cells are unique with respect to tyrosyl sulfotransferase activity. Furthermore, the marginal sulphation may explain the high proportion of gastrin-34 versus gastrin-17 in the equine antrum, since tyrosyl sulphation has been shown to promote the endoproteolytic processing of prohormones.
Department of Clinical Biochemistry, Rigshospitalet, The National University Hospital, Copenhagen, Denmark. johnsen@rh.dk
A H
AH
Johnsen
A
A
Sandin
I J
IJ
Rourke
J R
JR
Bundgaard
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G
Nilsson
J F
JF
Rehfeld
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004759:Enterochromaffin Cells / Q000201:enzymology*; D005753:Gastric Mucosa / Q000166:cytology* / Q000201:enzymology; D005755:Gastrins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006736:Horses; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011706:Pyloric Antrum; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015238:Sulfotransferases / Q000378:metabolism*; D013552:Swine
D005755:Gastrins; D011498:Protein Precursors; C013706:big gastrin; C042873:preprogastrin; D015238:Sulfotransferases; C039079:protein-tyrosine sulfotransferase