title: Mutagenesis of Phe381 and Phe382 in the extracellular domain of the insulin receptor: effects on receptor biosynthesis, processing, and ligand-dependent internalization.
abstract: Mutations of the extracellular domain of the insulin receptor impair processing and transport of receptors to the plasma membrane. We have previously reported that a mutation substituting Val for Phe382 in the alpha-subunit of the insulin receptor impairs intracellular processing and insulin-induced autophosphorylation of the mutant receptor. In this investigation, we have generated two independent mutations of amino acids Phe381 and Phe382 of the insulin receptor: Val for Phe381 and Leu for Phe382. These substitutions cause a slight impairment of intracellular processing and transport of the mutant receptors. Furthermore, insulin-dependent internalization of the mutant receptors is unaffected by these mutations. Thus, of the three substitutions studied to date, Val for Phe382 is the only mutation of the Phe381-Phe382 sequence that causes a major defect in post-translational processing of the receptor.
authors.affiliation: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892.
authors.forename: D
authors.initials: D
authors.lastname: Accili
authors.forename: L
authors.initials: L
authors.lastname: Mosthaf
authors.forename: R
authors.initials: R
authors.lastname: Levy-Toledano
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
authors.forename: S I
authors.initials: SI
authors.lastname: Taylor
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D007328:Insulin; D008024:Ligands; D010649:Phenylalanine; D011972:Receptor, Insulin