Linked Life Data

18310296

Source:http://linkedlifedata.com/resource/pubmed/id/18310296

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-3-3
pubmed:abstractText
The interaction of gastrin with the cholecystokinin 2 (CCK2)/gastrin receptor has been studied extensively in relation to gastric acid secretion. However, not much is known about the contribution of individual amino acids of gastrin interacting with the CCK2 receptor, when gastrin is acting as a tumor growth factor. The purpose of the present study was to determine the significance of each individual amino acid residue of human gastrin-17 with respect to CCK2 receptor-mediated cell proliferation. Activation of this receptor was assessed using an in vitro bioassay based on gastrin-induced expression of a c-fos-luciferase reporter, transfected in AR42JB13 and Colo 320 cells, a rat pancreatic and human colorectal cell line respectively. Gastrin-17 dose dependently increased c-fos induction in both cancer cell lines. L365,260, a known CCK2 receptor antagonist, completely blocked the gastrin signal, demonstrating the specificity of this assay. We demonstrated for the first time that four carboxy-terminal amino acids of gastrin-17 are essential for activation of the CCK2 receptor with respect to c-fos induction. Also other residues of gastrin-17, notably glycine-2 for the rat CCK2 receptor and glutamic acid 8-10 and tyrosine-12 for the human receptor, were found to be important, although to a lesser extent. Alanine-substitution variants of each of the four carboxy-terminal amino acids of gastrin-17 showed strongly reduced receptor activation but did not act as competitive inhibitors of gastrin-17. Identification of the essential role of the carboxy-terminal tetrapeptide of gastrin-17 in CCK2 receptor-mediated c-fos induction indicates that gastrin inhibitory therapeutic strategies should mainly be targeted toward this region of gastrin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1351-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18310296-Alanine, pubmed-meshheading:18310296-Amino Acid Substitution, pubmed-meshheading:18310296-Animals, pubmed-meshheading:18310296-Cell Proliferation, pubmed-meshheading:18310296-Colorectal Neoplasms, pubmed-meshheading:18310296-DNA Primers, pubmed-meshheading:18310296-Gastrins, pubmed-meshheading:18310296-Genes, fos, pubmed-meshheading:18310296-Humans, pubmed-meshheading:18310296-Luciferases, pubmed-meshheading:18310296-Pancreatic Neoplasms, pubmed-meshheading:18310296-Pentagastrin, pubmed-meshheading:18310296-Promoter Regions, Genetic, pubmed-meshheading:18310296-Protein Precursors, pubmed-meshheading:18310296-RNA, Messenger, pubmed-meshheading:18310296-Rats, pubmed-meshheading:18310296-Receptor, Cholecystokinin B, pubmed-meshheading:18310296-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18310296-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
Characterization of gastrin-cholecystokinin 2 receptor interaction in relation to c-fos induction.
pubmed:affiliation
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Lundlaan 6, Utrecht, The Netherlands. m.j.hollestelle@umcutrecht.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't