title: Ligand-induced ErbB receptor dimerization.
abstract: Structural studies have provided important new insights into how ligand binding promotes homodimerization and activation of the EGF receptor and the other members of the ErbB family of receptor tyrosine kinases. These structures have also suggested possible explanations for the unique properties of ErbB2, which has no known ligand and can cause cell transformation (and tumorigenesis) by simple overexpression. In parallel with these advances, studies of the EGF receptor at the cell surface increasingly argue that the structural studies are missing key mechanistic components. This is particularly evident in the structural prediction that EGF binding linked to receptor dimerization should be positively cooperative, whereas cell-surface EGF-binding studies suggest negative cooperativity. In this review, I summarize studies of ErbB receptor extracellular regions in solution and of intact receptors at the cell surface, and attempt to reconcile the differences suggested by the two approaches. By combining results obtained with receptor 'parts', it is qualitatively possible to explain some models for the properties of the whole receptor. These considerations underline the need to consider the intact ErbB receptors as intact allosterically regulated enzymes, and to combine cellular and structural studies into a complete picture.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6059, USA. mlemmon@mail.med.upenn.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lemmon
mesh_terms: D000818:Animals; D019281:Dimerization; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018739:Oncogene Proteins v-erbB / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008024:Ligands; D018739:Oncogene Proteins v-erbB; D066246:ErbB Receptors