| pubmed-article:16522741 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0174680 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0167117 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C1414685 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0013879 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:16522741 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:16522741 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:16522741 | pubmed:dateCreated | 2006-3-8 | lld:pubmed |
| pubmed-article:16522741 | pubmed:abstractText | Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and beta-cell proliferation. This study aimed to investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic beta-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position -48; 5'-TAACGTCA-3') of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying beta-cell proliferation by EX. | lld:pubmed |
| pubmed-article:16522741 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16522741 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16522741 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16522741 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16522741 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16522741 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:16522741 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16522741 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16522741 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:16522741 | pubmed:issn | 0022-0795 | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:PaiR RRR | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:YoonS HSH | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:MerzJJ | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:LUS CSC | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:HahnS JSJ | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:ZheH XHX | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:KimM-JMJ | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:KuWeiW | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:KangJ-HJH | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:ORRF GFG | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:JeongI-KIK | lld:pubmed |
| pubmed-article:16522741 | pubmed:author | pubmed-author:RhieD-JDJ | lld:pubmed |
| pubmed-article:16522741 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16522741 | pubmed:volume | 188 | lld:pubmed |
| pubmed-article:16522741 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16522741 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16522741 | pubmed:pagination | 623-33 | lld:pubmed |
| pubmed-article:16522741 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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| pubmed-article:16522741 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16522741 | pubmed:articleTitle | Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element. | lld:pubmed |
| pubmed-article:16522741 | pubmed:affiliation | Departments of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. | lld:pubmed |
| pubmed-article:16522741 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16522741 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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