title: Ligand regulation of a constitutively dimeric EGF receptor.
abstract: Ligand-induced receptor dimerization has traditionally been viewed as the key event in transmembrane signalling by epidermal growth factor receptors (EGFRs). Here we show that the Caenorhabditis elegans EGFR orthologue LET-23 is constitutively dimeric, yet responds to its ligand LIN-3 without changing oligomerization state. SAXS and mutational analyses further reveal that the preformed dimer of the LET-23 extracellular region is mediated by its domain II dimerization arm and resembles other EGFR extracellular dimers seen in structural studies. Binding of LIN-3 induces only minor structural rearrangements in the LET-23 dimer to promote signalling. Our results therefore argue that EGFR can be regulated by allosteric changes within an existing receptor dimer--resembling signalling by insulin receptor family members, which share similar extracellular domain compositions but form covalent dimers.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 322A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Freed
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 322A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarado
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 322A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lemmon
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D004331:Drosophila melanogaster; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands
chemical_list: D008024:Ligands; D066246:ErbB Receptors