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http://purl.uniprot.org/citations/16926376http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16926376http://www.w3.org/2000/01/rdf-schema#comment"Glucagon-like peptide-1 and its potent agonist exendin-4 induce several immediate early response genes (IEGs) that code for transcription factors implicated in cell proliferation, differentiation, and apoptosis. We recently observed that early growth response factor-1 (EGR-1), an IEG product, was required for transcriptional activation of Ccnd1 (cyclin D1) gene by exendin-4. Herein, the regulatory mechanism whereby exendin-4 activates the transcription of EGR-1 gene was investigated in the pancreatic beta-cell line INS-1. Deletion analysis of rat EGR-1 promoter identified a critical region between -73 and -46 for the activation of EGR-1 in response to exendin-4. Mutation of the proximal putative cAMP response element (CRE, 5'-GTACGTCA-3') located at -69 resulted in a significant decrease in the EGR-1 transcription, whereas the mutation of the distal putative CRE at -139 was without such an effect. In immune supershift assays using exendin-4-treated cells, binding of cAMP response element-binding protein (CREB) phosphorylated on Ser(133) to the proximal CRE was increased. Employment of a CREB mutant containing Ala substitution at Ser(133) or a dominant negative CREB mutant that inhibits the binding of endogenous CREB to DNA significantly decreased the exendin-4-induced EGR-1 transcription. In experiments using specific protein kinase inhibitors, the effect of H-89 was more prominent than PD-98059, indicating the predominance of the PKA signaling over the MEK/ERK in induction of EGR-1. Therefore, it appears that the proximal CRE site is critical and the binding with CREB phosphorylated on Ser(133) is necessary for induction of the EGR-1 transcription by exendin-4."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.org/dc/terms/identifier"doi:10.1152/ajpendo.00181.2006"xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Kim M.J."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Yoon S.H."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Kim M.S."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Kang J.H."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Koh K.H."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Jo Y.H."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Hahn S.J."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Rhie D.J."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Jang H.I."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/author"Yum K.S."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/name"Am J Physiol Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/pages"E215-22"xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/title"Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene."xsd:string
http://purl.uniprot.org/citations/16926376http://purl.uniprot.org/core/volume"292"xsd:string
http://purl.uniprot.org/citations/16926376http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16926376
http://purl.uniprot.org/citations/16926376http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16926376
http://purl.uniprot.org/uniprot/#_A6J2W7-mappedCitation-16926376http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16926376
http://purl.uniprot.org/uniprot/#_P97705-mappedCitation-16926376http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16926376
http://purl.uniprot.org/uniprot/#_P08154-mappedCitation-16926376http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16926376
http://purl.uniprot.org/uniprot/A6J2W7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/16926376
http://purl.uniprot.org/uniprot/P97705http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/16926376