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)

Bombesin and structurally related peptides including gastrin releasing peptide (GRP) are potent mitogens for Swiss 3T3 cells. The early cellular and molecular responses elicited by bombesin and structurally related peptides have been elucidated in detail. Further understanding of the molecular basis of the potent mitogenic response initiated by bombesin is required in order to elucidate the mechanism by which the occupied receptor communicates with effector molecules in the cell. Transmembrane signalling mechanisms involving either a tyrosine kinase or a guanine nucleotide-binding regulatory protein (G protein) have been proposed. Here we summarize our experimental evidence indicating that a G protein(s) is involved in the coupling of the bombesin receptor to the generation of intracellular signals related to mitogenesis. Evidence for the role of G proteins in bombesin signal transduction pathways has been obtained by assessing the effects of guanine nucleotide analogues on both receptor-mediated responses in permeabilized cells and ligand binding in membrane preparations. We found that [125I]GRP-receptor complexes were solubilized from Swiss 3T3 cell membranes by using the detergents taurodeoxycholate or deoxycholate. Addition of guanosine 5-[gamma-thio]triphosphate (GTP gamma S) to ligand-receptor complexes isolated by gel filtration enhanced the rate of ligand dissociation in a concentration-dependent and nucleotide-specific manner. These results demonstrate the successful solubilization of [125I]GRP-receptor complexes from Swiss 3T3 cell membranes and provide evidence for the physical association between the ligand-receptor complex and a guanine nucleotide binding protein(s).
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PMID:Mitogenic signalling through the bombesin receptor: role of a guanine nucleotide regulatory protein. 196 86

A review of the literature encompassing numerous pharmacological, physiological, and biochemical studies indicates the presence of at least four CCK receptor types, CCKA, CCKB, gastrin, and CG-4 receptors. Multiple subtypes of the CCKAR have been postulated to account for the differences in pharmacology or affinity cross-linking of CCKARs between pancreas and gallbladder and the presence of high and low affinity CCKARs on pancreatic acini. Multiple subtypes of the CCKBR have been postulated to explain the differences in pharmacology and physiology between gastric and gallbladder smooth muscle CCKBRs. We recently cloned and functionally expressed both the CCKAR and the CCKBR from rat, guinea pig, and human. The CCKAR and CCKBR are 48% homologous and constitute a family of receptors within the guanine nucleotide-binding regulatory protein-coupled superfamily of receptors. Each receptor is highly conserved between species. A single cDNA encoding a single protein is present in both pancreas and gallbladder and can account for both high and low affinity CCKARs found on pancreatic acini when transfected into COS-7 cells. A single cDNA encoding a single CCKBR protein is present in both the central nervous system and the periphery including the gastrointestinal system. Therefore, the gastrin receptor is actually a CCKBR present on parietal cells. Genomic and cDNA library hybridization as well as Northern and Southern hybridization studies among rat, guinea pig, and human species identifies only two members of the CCK receptor family, CCKAR and CCKBR. Although these studies do not identify other closely related members of the CCK receptor family, they do not rule out the existence of other less closely related members. Furthermore, differences in tissue and species-specific posttranslational processing, receptor coupling, and associated membrane protein and lipid heterogeneity may be among some of the other factors that may account for the phenotypic expression of more receptor subtypes than molecular studies would predict.
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PMID:Cholecystokinin receptor family. Molecular cloning, structure, and functional expression in rat, guinea pig, and human. 818 15