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http://purl.uniprot.org/citations/12138094http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12138094http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12138094http://www.w3.org/2000/01/rdf-schema#comment"The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) have a highly homologous structure, but different biological effects. Insulin and IGF-I half-receptors can heterodimerize, leading to the formation of insulin/IGF-I hybrid receptors (Hybrid-Rs) that bind IGF-I with high affinity. As the IR exists in two isoforms (IR-A and IR-B), we evaluated whether the assembly of the IGF-IR with either IR-A or IR-B moieties may differently affect Hybrid-R signaling and biological role. Three different models were studied: (a) 3T3-like mouse fibroblasts with a disrupted IGF-IR gene (R(-) cells) cotransfected with the human IGF-IR and with either the IR-A or IR-B cDNA; (b) a panel of human cell lines variably expressing the two IR isoforms; and (c) HepG2 human hepatoblastoma cells predominantly expressing either IR-A or IR-B, depending on their differentiation state. We found that Hybrid-Rs containing IR-A (Hybrid-Rs(A)) bound to and were activated by IGF-I, IGF-II, and insulin. By binding to Hybrid-Rs(A), insulin activated the IGF-I half-receptor beta-subunit and the IGF-IR-specific substrate CrkII. In contrast, Hybrid-Rs(B) bound to and were activated with high affinity by IGF-I, with low affinity by IGF-II, and insignificantly by insulin. As a consequence, cell proliferation and migration in response to both insulin and IGFs were more effectively stimulated in Hybrid-R(A)-containing cells than in Hybrid-R(B)-containing cells. The relative abundance of IR isoforms therefore affects IGF system activation through Hybrid-Rs, with important consequences for tissue-specific responses to both insulin and IGFs."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m202766200"xsd:string
http://purl.uniprot.org/citations/12138094http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m202766200"xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Belfiore A."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Belfiore A."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Vigneri R."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Vigneri R."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Frasca F."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Frasca F."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Mineo R."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Mineo R."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Pandini G."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Pandini G."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Sciacca L."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/author"Sciacca L."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/pages"39684-39695"xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/pages"39684-39695"xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/title"Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved."xsd:string
http://purl.uniprot.org/citations/12138094http://purl.uniprot.org/core/title"Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved."xsd:string