title: Ligand-induced transformation by a noninternalizing epidermal growth factor receptor.
abstract: Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided a genetic probe to investigate the role of internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective receptor exhibited a normal mitogenic response at significantly lower ligand concentrations than did cells expressing wild-type receptors. A transformed phenotype and anchorage-independent growth were observed at ligand concentrations that failed to elicit these responses in cells expressing wild-type receptors. These findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF. Thus, downregulation can serve as an attenuation mechanism, without which transformation ensues.
authors.affiliation: Department of Pathology, University of California-San Diego, La Jolla 92093.
authors.forename: A
authors.initials: A
authors.lastname: Wells
authors.forename: J B
authors.initials: JB
authors.lastname: Welsh
authors.forename: C S
authors.initials: CS
authors.lastname: Lazar
authors.forename: H S
authors.initials: HS
authors.lastname: Wiley
authors.forename: G N
authors.initials: GN
authors.lastname: Gill
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D002455:Cell Division; D002460:Cell Line; D015536:Down-Regulation; D004705:Endocytosis; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D008979:Moloney murine leukemia virus / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014162:Transfection
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases