Comparative analysis of the signaling capabilities of the insulin receptor-related receptor |
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Authors: | Klammt Jürgen Garten Antje Barnikol-Oettler Anja Beck-Sickinger Annette G Kiess Wieland |
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Affiliation: | Hospital for Children and Adolescents, University of Leipzig, 04317 Leipzig, Oststrasse 21-25, Germany. juergen.klammt@medizin.uni-leipzig.de |
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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. |
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Keywords: | IRR Insulin receptor IGF-I receptor Tyrosine phosphorylation Signal transduction |
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