title: Comparative analysis of the signaling capabilities of the insulin receptor-related receptor.
abstract: Although insulin receptor (InsR) and type I insulin-like growth factor receptor (IGF-IR) elicit different physiological effects in their target tissues, their signaling capabilities are similar to a large extent. In the present work, we investigated the potential of the third member of the family, insulin receptor-related receptor (IRR), to associate with known interaction partners of the InsR and the IGF-I receptor in a yeast two-hybrid assay. Using the intracellular part of the IRR we found no association with any of the tested signaling molecules. Phosphotyrosine detection revealed a lack in the constitutive activation of the IRR described for analogous constructs of the two other members of the family. Replacement of the kinase domain of the IGF-IR or its C-terminal lobe alone into the IRR caused a complete restoration of the tyrosine phosphorylation of the IRR. The reestablishment of autophosphorylation was paralleled by restoration of interaction with a specific range of signaling molecules.
authors.affiliation: Hospital for Children and Adolescents, University of Leipzig, 04317 Leipzig, Oststrasse 21-25, Germany. juergen.klammt@medizin.uni-leipzig.de <juergen.klammt@medizin.uni-leipzig.de>
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Antje
authors.initials: A
authors.lastname: Garten
authors.forename: Anja
authors.initials: A
authors.lastname: Barnikol-Oettler
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
mesh_terms: D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C066542:insulin receptor-related receptor