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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-27
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pubmed:abstractText |
The gastric hormone gastrin regulates the expression of a variety of genes involved in control of acid secretion and also in the growth and organization of the gastric mucosa. One putative target is plasminogen activator inhibitor-2 (PAI-2), which is a component of the urokinase activator system that acts extracellularly to inhibit urokinase plasminogen activator (uPA) and intracellularly to suppress apoptosis. Previous studies have demonstrated that gastrin induces PAI-2 both in gastric epithelial cells expressing the gastrin (CCK-2) receptor and, via activation of paracrine networks, in adjacent cells that do not express the receptor. We have now sought to identify the response element(s) in the PAI-2 promoter targeted by paracrine mediators initiated by gastrin. Mutational analysis identified two putative response elements in the PAI-2 promoter that were downstream of gastrin-activated paracrine signals. One was identified as a putative MAZ site, mutation of which dramatically reduced both basal and gastrin-stimulated responses of the PAI-2 promoter by a mechanism involving PGE(2) and the small GTPase RhoA. Yeast one-hybrid screening identified the other as binding the activating signal cointegrator-1 (ASC-1) complex, which was shown to be the target of IL-8 released by gastrin. RNA interference (RNAi) knockdown of two subunits of the ASC-1 complex (p50 and p65) inhibited induction of PAI-2 expression by gastrin. The data reveal previously unsuspected transcriptional mechanisms activated as a consequence of gastrin-triggered paracrine networks and emphasize the elaborate and complex cellular control mechanisms required for a key component of tissue responses to damage and infection.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-10454579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-10611152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-10622253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-10949579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11004477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11018526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11113118,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11181951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11192947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-11518686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12010885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12077347,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12105855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12372397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12388195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12390891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12488236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12761119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12808021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12891554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-12891702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-1454839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-14647423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-14996729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-1502157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-15778736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-15780477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-1650454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-16923810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-17442673,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-17604853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-18395088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-2432970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-2434595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-2908509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-3045756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-7776974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-7831396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-8132812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-8229845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-8916932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-9037208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-9212216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19074642-9852054
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Gastrins,
http://linkedlifedata.com/resource/pubmed/chemical/IL8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 2,
http://linkedlifedata.com/resource/pubmed/chemical/RHOA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/TRIP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/c-MYC-associated zinc finger protein,
http://linkedlifedata.com/resource/pubmed/chemical/gastrin 17,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G414-23
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pubmed:dateRevised |
2010-9-22
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pubmed:meshHeading |
pubmed-meshheading:19074642-Humans,
pubmed-meshheading:19074642-Gastric Mucosa,
pubmed-meshheading:19074642-Mutation,
pubmed-meshheading:19074642-Gastrins,
pubmed-meshheading:19074642-Base Sequence,
pubmed-meshheading:19074642-Binding Sites,
pubmed-meshheading:19074642-Molecular Sequence Data,
pubmed-meshheading:19074642-Cell Line, Tumor,
pubmed-meshheading:19074642-Dinoprostone,
pubmed-meshheading:19074642-Signal Transduction,
pubmed-meshheading:19074642-DNA-Binding Proteins
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