title: Transphosphorylation as a possible mechanism for insulin and epidermal growth factor receptor activation.
abstract: Fully functional chimeric receptors, consisting of major epidermal growth factor and insulin receptor domains, were co-expressed with kinase-negative epidermal growth factor and insulin receptor mutants in human kidney fibroblasts. Under these conditions, homologous extracellular and cytoplasmic domains mediated association of receptors and their precursors. The significance of receptor-receptor interaction was confirmed by transphosphorylation of kinase-negative receptors by ligand-activated chimeric receptors, which was observed between receptors sharing the same cytoplasmic domain as well as between receptors bearing only the same extracellular domain and containing heterologous kinases. Furthermore, the impaired ligand internalization capacity of a kinase-deficient insulin receptor was partially restored by transphosphorylation. Our experiments suggest interreceptor transphosphorylation and transactivation as a possible mechanism for signal amplification.
authors.affiliation: Max-Planck Institut für Biochemie, Martinsried, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lammers
authors.forename: E
authors.initials: E
authors.lastname: Van Obberghen
authors.forename: R
authors.initials: R
authors.lastname: Ballotti
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D002460:Cell Line; D002678:Chimera; D003001:Cloning, Molecular; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D008024:Ligands; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D008024:Ligands; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin