title: Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant.
abstract: Insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) are both from the same subgroup of receptor tyrosine kinases that exist as covalently bound receptor dimers at the cell surface. For both IR and IGF-IR, the most described forms are homodimer receptors. However, hybrid receptors consisting of one-half IR and one-half IGF-IR are also present at the cell surface. Two splice variants of IR are expressed that enable formation of two isoforms of the IGF-IR/IR hybrid receptor. In this study, these two splice variants of hybrid receptors were studied with respect to binding affinities of insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II). Unlike previously published data, in which semipurified receptors have been studied, we found that the two hybrid receptor splice variants had similar binding characteristics with respect to insulin, IGF-I, and IGF-II binding. We studied both semipurified and purified hybrid receptors. In all cases we found that IGF-I had at least 50-fold higher affinity than insulin, irrespective of the splice variant. The binding characteristics of insulin and IGF-I to both splice variants of the hybrid receptors were similar to classical homodimer IGF-IR.
authors.affiliation: Novo Nordisk A/S, Novo Allé, DK-2880 Bagsvaerd, Denmark. risl@novonordisk.com
authors.forename: Rita
authors.initials: R
authors.lastname: Slaaby
authors.forename: Lauge
authors.initials: L
authors.lastname: Schäffer
authors.forename: Inger
authors.initials: I
authors.lastname: Lautrup-Larsen
authors.forename: Asser Sloth
authors.initials: AS
authors.lastname: Andersen
authors.forename: Allan Christian
authors.initials: AC
authors.lastname: Shaw
authors.forename: Ida Stenfeldt
authors.initials: IS
authors.lastname: Mathiasen
authors.forename: Jakob
authors.initials: J
authors.lastname: Brandt
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005091:Exons; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D007328:Insulin; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin