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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#_4 http://www.w3.org/ns/prov#value Cotransfection of the reporter genes with truncated versions of the ER shows that the two non-ligand activators of ER require different regions of the receptor to produce their effects on transcription. EGF acts primarily by means of transactivation domain AF-1, whereas cAMP acts via transactivation domain AF-2 of the ER. A point mutation that removes a major site of inducible phosphorylation within the AF-1 domain of the ER abolishes the response to EGF, but the response to estradiol and cAMP is retained. Specific inhibition of cAMP-activated protein kinase (protein kinase A) prevents the response to elevated cAMP but does not affect EGF or estradiol responses. Overexpression of the protein kinase A catalytic subunit in HeLa cells results in an amplified response to estradiol, similar to that induced by cholera toxin with 3-isobutyl-1-methyl-xanthine. Comparable experiments performed using COS-1 cells produce similar results but also reveal cell type- and promoter-specific aspects of the activation mechanisms. Apparently, the ER may be activated by three different signal molecules, estradiol, EGF, and cAMP, each using a mechanism that is distinguishable from that of the others. http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/9178752 http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/9178752 http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#_4 http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA#pubinfo http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA http://purl.org/dc/terms/created 2014-07-03T14:30:58.399+02:00 http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAf5Gjgek57K4nGLzYOImM0IInXqRxjJtomL9ZCMzzTuA http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234