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All rights reserved." } ], "http://purl.org/dc/elements/1.1/title" : [ { "@value" : "BEL Framework Large Corpus Document" } ], "http://purl.org/pav/authoredBy" : [ { "@id" : "http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_4" } ], "http://purl.org/pav/version" : [ { "@value" : "1.4" } ] }, { "@id" : "http://www.tkuhn.ch/bel2nanopub/RAclys_jJeAqY97gF95D2dhTnlK5xml09QJM62RGcIWes#_3", "http://www.w3.org/ns/prov#value" : [ { "@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. 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