Binding of progastrin fragments to the 78 kDa gastrin-binding protein.
The non-selective gastrin/cholecystokinin receptor antagonists proglumide and benzotript inhibit colon carcinoma cell proliferation by binding to the 78 kDa gastrin-binding protein (GBP) (Baldwin, Proc. Natl. Acad. Sci. USA, 91 (1994) 7593-7597). However, although most colon carcinoma cell lines synthesize progastrin, production of mature amidated gastrin17 has not been observed. In order to define the structural requirements for the binding of gastrin to the GBP the affinities of various fragments of amidated and C-terminally extended gastrin17 for the GBP have been measured. The results indicate that the GBP recognizes both N- and C-termini of gastrin17. Moreover since C-terminal amidation is not a prerequisite for binding of gastrin to the GBP, the GBP is a potential target for the autocrine effects of progastrin.
Baldwin
G S
GS
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, P.O. Royal Melbourne Hospital, Victoria, Australia.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000473:pathology; D003432:Cross-Linking Reagents; D005755:Gastrins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D063991:Mitochondrial Trifunctional Protein; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D013552:Swine
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D005755:Gastrins; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D011498:Protein Precursors; C013706:big gastrin; C037857:gastrin heptadecapeptide, Nle(15)-; D063991:Mitochondrial Trifunctional Protein