| http://purl.uniprot.org/citations/11500939 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11500939 | http://www.w3.org/2000/01/rdf-schema#comment | "Insulin-like growth factor II (IGF-II) plays a key role in mitogenesis during development and tumorigenesis and is believed to exert its mitogenic functions mainly through the IGF-I receptor. Recently, we identified the insulin receptor isoform A (IR(A)) as an additional high affinity receptor for IGF-II in both fetal and cancer cells. Here we investigated the mitogenic signaling of IGF-II via the Akt/Glycogen synthase kinase 3 (Gsk3) axis employing R-IR(A) cells that are IGF-I receptor null mouse embryonic fibroblasts expressing the human IR(A). IGF-II induced activation of the proto-oncogenic serine kinase Akt, reaching maximal at 5-10 min. IGF-II also caused the rapid and sustained deactivation of glycogen synthase kinase 3-beta (Gsk3beta), reaching maximal at 1-3 min, shortly preceding, therefore, maximal activation of Akt. Under our conditions, IGF-II and insulin induced 70-80% inhibition of Gsk3betaactivity. In these cells IGF-II also deactivated Gsk3alpha although less effectively than Gsk3beta. In parallel experiments, we found that IGF-II induced transient activation of extracellular-signal-regulated kinases (Erk) reaching maximal at 5-10 min and decreasing thereafter. Time courses and potencies of regulation of both mitogenic pathways (Akt/Gsk3beta and Erk) by IGF-II via IR(A) were similar to those of insulin. Furthermore, IGF-II like insulin effectively stimulated cell cycle progression from the G0/G1 to the S and G2/M phases. Interestingly, AP-1-mediated gene expression, that was reported to be negatively regulated by Gsk3beta was only weakly increased after IGF-II stimulation. Our present data suggest that the coordinated activation or deactivation of Akt, Gsk3beta, and Erk may account for IGF-II mitogenic effects and support an active role for IR(A) in IGF-II action."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.org/dc/terms/identifier | "doi:10.1002/jcb.1196"xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/author | "Comai L."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/author | "Vigneri R."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/author | "Scalia P."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/author | "Sung C.K."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/author | "Heart E."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/name | "J Cell Biochem"xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/pages | "610-618"xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/title | "Regulation of the Akt/Glycogen synthase kinase-3 axis by insulin-like growth factor-II via activation of the human insulin receptor isoform-A."xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://purl.uniprot.org/core/volume | "82"xsd:string |
| http://purl.uniprot.org/citations/11500939 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11500939 |
| http://purl.uniprot.org/citations/11500939 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11500939 |
| http://purl.uniprot.org/uniprot/P01344#attribution-657FE6BCE396F30AA7E9B648D8494C90 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/11500939 |
| http://purl.uniprot.org/uniprot/P01308#attribution-657FE6BCE396F30AA7E9B648D8494C90 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/11500939 |
| http://purl.uniprot.org/uniprot/P06213#attribution-2192544B94C83AE196F73FF71EDFBCCB | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/11500939 |