title: Cys 786 and Cys 776 in the posttranslational processing of the insulin and IGF-I receptors.
abstract: The extracellular regions of insulin and IGF-I receptors (IR and IGF-IR) contain fibronectin type III repeats with cysteine residues potentially involved in S==S bond. In this report we show that Cys 786 in the IR and the corresponding Cys 776 in the IGF-IR regulate proreceptor dimerization with high specificity. Both C786S insulin and C776S IGF-I proreceptors reach the monomeric 210-kDa step, but do not proceed further. Mature IR(C786S) and IGF-IR(C776S) expression on plasmamembrane is abolished. No retention of C786S IR precursor was detected in the endoplasmic reticulum, which is degraded by a nonlysosomal mechanism. The rearrangement of the remaining cysteines in the insulin receptor beta subunit ectodomain does not rescue dimerization of C786S insulin proreceptor. As observed in other transmembrane receptors, iuxtamembrane cysteines, specifically Cys 786 in the IR and Cys 776 in the IGF-IR, are critical for correct processing of proreceptors.
authors.affiliation: Department of Endocrinology and Metabolism, University of Genova, Genova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Maggi
authors.forename: R
authors.initials: R
authors.lastname: Cordera
mesh_terms: D000818:Animals; D019556:COS Cells; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017526:Receptor, IGF Type 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D007328:Insulin; D021122:Protein Subunits; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D003545:Cysteine