Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A 78 kDa protein (p78) has been partially purified from washed membranes isolated from the corpus of porcine gastric mucosa. The purification was monitored by covalent cross-linking of iodinated [Nle15]-gastrin. 2. A single N-terminal sequence extending for 33 amino acids was obtained from the p78 preparation. Partial sequences totalling 192 amino acids were also obtained from 14 tryptic and 3 Staphylococcal V8 peptides. 3. 10 peptides plus the N-terminal sequence were derived from a previously unsequenced protein which was distantly related to the product of the E. coli fadB gene (Baldwin G. S. (1993) Comp. Biochem. Physiol. 104B, 55-61). The remaining 7 peptides were derived from the beta-subunit of the gastric H+/K(+)-ATPase. 4. The gastrin-binding activity remained in association with p78, and could be separated from the beta-subunit of the gastric H+/K(+)-ATPase, during chromatography on tomato lectin-Sepharose. 5. We conclude that p78 binds gastrin, and is a novel member of the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase family of enzymes.
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PMID:Isolation and partial amino acid sequence of a 78 kDa porcine gastrin-binding protein. 801 37

Inhibition of colon carcinoma cell growth by the nonselective gastrin/cholecystokinin (CCK) receptor antagonists proglumide and benzotript provided evidence that gastrin functions as an autocrine growth factor. However, the molecular properties of the receptor mediating the antagonist effects have not been identified. A 78-kDa gastrin-binding protein (GBP), the sequence of which is related to the family of enzymes possessing enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities, has been previously purified from porcine gastric mucosal membranes. I now report that covalent cross-linking of 125I-labeled [Nle15]gastrin2,17 to the 78-kDa GBP is inhibited by crotonyl-CoA and by acetoacetyl-CoA. Gastrin, CCK, and their analogues also inhibit cross-linking, and the spectrum of analogue affinities correlates better with the values previously reported for binding to the gastrin/CCK-C receptor than with the values reported for binding to either the CCK-A or the gastrin/CCK-B receptor. Cross-linking is also inhibited by proglumide and benzotript, but no inhibition is seen with either the CCK-A receptor-selective antagonist L364,718 or the gastrin/CCK-B receptor-selective antagonist L365,260. The affinities of antagonists for the GBP correlate well with their affinities for the gastrin/CCK-C receptor and with their potencies for inhibition of colon carcinoma cell growth. I conclude that the 78-kDa gastrin-binding protein is (i) a member of the hydratase/dehydrogenase family of fatty acid oxidation enzymes, (ii) the gastrin/CCK-C receptor, and (iii) the target for the antiproliferative action of two gastrin/CCK receptor antagonists.
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PMID:Antiproliferative gastrin/cholecystokinin receptor antagonists target the 78-kDa gastrin-binding protein. 805 25

The mitochondrial enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein (trifunctional protein) plays a major role in mitochondrial fatty acid oxidation. The enzyme complex consists of four molecules of alpha-subunit containing both hydratase and dehydrogenase domains and four molecules of beta-subunit containing the thiolase domain. The primary structure of a gastrin-binding protein (GBP) was highly homologous to that of the alpha-subunit of the trifunctional protein. Here, we report that gastrin inhibits the hydratase, dehydrogenase, and thiolase activities of the trifunctional protein. The gastrin/cholecystokinin receptor antagonist benzotript, which inhibited binding of gastrin to the GBP, also inhibited all three activities of the trifunctional protein. In addition, benzotript inhibits the activities of multifunctional enzymes having similar structures, such as the peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein and the Pseudomonas fragi fatty acid oxidation enzyme complex. This reagent, however, hardly inhibited various monofunctional enzymes involved in fatty acid oxidation.
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PMID:A new inhibitor of mitochondrial fatty acid oxidation. 882 58