title: The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs.
abstract: The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63.
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Scotland, United Kingdom.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Wiejak
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Scotland, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Dunlop
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Scotland, United Kingdom. Electronic address: stephen.yarwood@glasgow.ac.uk.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Yarwood
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D016755:Proto-Oncogene Proteins c-jun; C116122:RAPGEF3 protein, human; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018808:Transcription Factor AP-1
keywords: AP1; Cyclic AMP; EPAC1; SOCS3; Transcription; c-Jun