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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-11-27
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pubmed:abstractText |
Our previous work revealed that gastrin regulates chromogranin A (CgA) transcription through enhanced binding of Sp1, CREB and Egr-1 to a proximal gastrin-responsive promoter element (Gas-RE). Here, we provide a detailed characterization of the signalling pathways transmitting the effect of gastrin on the CgA promoter. Gastrin treatment of gastric AGS-B cells potently stimulated MEK-1 as well as MAP kinases ERK-1/-2, JNK and p38 in a time-dependent manner. Interruption of ERK-1/-2/MEK-1 pathways abolished the transactivating effect of gastrin, whereas blockade of JNK or p38 activity was without effect. Functional promoter analysis revealed that the minimal element CgA-85/-64 was sufficient and necessary to confer MEK-1/ERK responsiveness. Analysis of proximal signalling pathways showed that activation of the MEK-1/ERK-1/2 module by gastrin does not require Ras, PI3-kinase or intracellular calcium signals, but depends on activation of kinases of the PKC family. This report demonstrates that a pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor.
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pubmed:grant |
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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/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chromogranin A,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Gastrins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cholecystokinin B,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0898-6568
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
60-72
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17889508-Adenocarcinoma,
pubmed-meshheading:17889508-CREB-Binding Protein,
pubmed-meshheading:17889508-Calcium,
pubmed-meshheading:17889508-Cell Line, Tumor,
pubmed-meshheading:17889508-Chromogranin A,
pubmed-meshheading:17889508-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:17889508-Gastrins,
pubmed-meshheading:17889508-Gene Expression Regulation,
pubmed-meshheading:17889508-Humans,
pubmed-meshheading:17889508-MAP Kinase Kinase 1,
pubmed-meshheading:17889508-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17889508-Phosphorylation,
pubmed-meshheading:17889508-Protein Kinase C,
pubmed-meshheading:17889508-Receptor, Cholecystokinin B,
pubmed-meshheading:17889508-Signal Transduction,
pubmed-meshheading:17889508-Sp1 Transcription Factor,
pubmed-meshheading:17889508-Stomach Neoplasms
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pubmed:year |
2008
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pubmed:articleTitle |
Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB.
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pubmed:affiliation |
Laboratory for Angiogenesis and Tumor Metastasis, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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