http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#Head http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#provenance http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#pubinfo http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_1 http://purl.obolibrary.org/obo/RO_0002204 http://www.informatics.jax.org/marker/MGI:95295 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_33697 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://purl.obolibrary.org/obo/BFO_0000066 http://purl.bioontology.org/ontology/MSH/D005347 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10090 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_1 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://resource.belframework.org/belframework/1.0/namespace/selventa-legacy-chemical-names/serum%20insulin http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.w3.org/2000/01/rdf-schema#label a(SCHEM:"serum insulin") -> r(MGI:Egr1) http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#provenance http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. 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/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_3 http://www.w3.org/ns/prov#value The human insulin receptor (IR) exists in two isoforms (IR-A and IR-B). IR-A is a short isoform, generated by the skipping of exon 11, a small exon encoding for 12 amino acid residues at the carboxyl terminus of the IR alpha-subunit. Recently, we found that IR-A is the predominant isoform in fetal tissues and malignant cells and binds with a high affinity not only insulin but also insulin-like growth factor-II (IGF-II). To investigate whether the activation of IR-A by the two ligands differentially activate post-receptor molecular mechanisms, we studied gene expression in response to IR-A activation by either insulin or IGF-II, using microarray technology. To avoid the interfering effect of the IGF-IR, IGF-II binding to the IR-A was studied in IGF-IR-deficient murine fibroblasts (R- cells) transfected with the human IR-A cDNA (R-/IR-A cells). Gene expression was studied at 0.5, 3, and 8 h. We found that 214 transcripts were similarly regulated by insulin and IGF-II, whereas 45 genes were differentially transcribed. Eighteen of these differentially regulated genes were responsive to only one of the two ligands (12 to insulin and 6 to IGF-II). Twenty-seven transcripts were regulated by both insulin and IGF-II, but a significant difference between the two ligands was present at least in one time point. Interestingly, IGF-II was a more potent and/or persistent regulator than insulin for these genes. Results were validated by measuring the expression of 12 genes by quantitative real-time reverse transcriptase-PCR. In conclusion, we show that insulin and IGF-II, acting via the same receptor, may differentially affect gene expression in cells. These studies provide a molecular basis for understanding some of the biological differences between the two ligands and may help to clarify the biological role of IR-A in embryonic/fetal growth and the selective biological advantage that malignant cells producing IGF-II may acquire via IR-A overexpression. http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12881524 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12881524 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_3 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#pubinfo http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://purl.org/dc/terms/created 2014-07-03T14:30:14.956+02:00 http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234