title: Cytoplasmic domains determine signal specificity, cellular routing characteristics and influence ligand binding of epidermal growth factor and insulin receptors.
abstract: The cell surface receptors for insulin and epidermal growth factor (EGF) both employ a tyrosine-specific protein kinase activity to fulfil their distinct biological roles. To identify the structural domains responsible for various receptor activities, we have generated chimeric receptor polypeptides consisting of major EGF and insulin receptor structural domains and examined their biochemical properties and cellular signalling activities. The EGF-insulin receptor hybrids are properly synthesized and transported to the cell surface, where they form binding competent structures that are defined by the origin of their extracellular domains. While their ligand binding affinities are altered, we find that these chimeric receptors are fully functional in transmitting signals across the plasma membrane and into the cell. Thus, EGF receptor and insulin receptor cytoplasmic domain signalling capabilities are independent of their new heterotetrameric or monomeric environments respectively. Furthermore, the cytoplasmic domains carry the structural determinants that define kinase specificity, mitogenic and transforming potential, and receptor routing.
authors.affiliation: Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.
authors.forename: H
authors.initials: H
authors.lastname: Riedel
authors.forename: T J
authors.initials: TJ
authors.lastname: Dull
authors.forename: A M
authors.initials: AM
authors.lastname: Honegger
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002678:Chimera; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D008024:Ligands; D004247:DNA; D066246:ErbB Receptors; D011972:Receptor, Insulin; D013755:Tetradecanoylphorbol Acetate