@prefix dcterms: .
@prefix this: .
@prefix sub: .
@prefix beldoc: .
@prefix rdfs: .
@prefix rdf: .
@prefix xsd: .
@prefix dce: .
@prefix pav: .
@prefix np: .
@prefix belv: .
@prefix prov: .
@prefix schem: .
@prefix RNA: .
@prefix mgi: .
@prefix geneProductOf: .
@prefix mesh: .
@prefix occursIn: .
@prefix species: .
@prefix pubmed: .
@prefix orcid: .
sub:Head {
this: np:hasAssertion sub:assertion;
np:hasProvenance sub:provenance;
np:hasPublicationInfo sub:pubinfo;
a np:Nanopublication .
}
sub:assertion {
sub:_1 geneProductOf: mgi:95296;
a RNA: .
sub:_2 occursIn: mesh:D005347, species:10090;
rdf:object sub:_1;
rdf:predicate belv:increases;
rdf:subject schem:serum%20insulin;
a rdf:Statement .
sub:assertion rdfs:label "a(SCHEM:\"serum insulin\") -> r(MGI:Egr2)" .
}
sub:provenance {
beldoc: dce:description "Approximately 61,000 statements.";
dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
dce:title "BEL Framework Large Corpus Document";
pav:authoredBy sub:_4;
pav:version "1.4" .
sub:_3 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.";
prov:wasQuotedFrom pubmed:12881524 .
sub:_4 rdfs:label "Selventa" .
sub:assertion prov:hadPrimarySource pubmed:12881524;
prov:wasDerivedFrom beldoc:, sub:_3 .
}
sub:pubinfo {
this: dcterms:created "2014-07-03T14:30:14.957+02:00"^^xsd:dateTime;
pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}