title: Emerging concepts in the regulation of the EGF receptor and other receptor tyrosine kinases.
abstract: The activation of receptor tyrosine kinases in response to extracellular signals is a principal component of metazoan signaling. Structural analysis of the extracellular and intracellular domains of these receptors has shed substantial light on the mechanisms underlying their activation. A remaining challenge is to understand how these domains operate together in the context of the full-length receptors. With a focus on the epidermal growth factor (EGF) receptor, this review highlights recent advances towards this goal. Although receptor tyrosine kinases are divergent in terms of the details of how they operate, these studies reveal common mechanisms that ensure activation in the proper context. Understanding these mechanisms provides insights into the vulnerabilities of these receptors to disease-causing mutations.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Endres
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Tiago
authors.initials: T
authors.lastname: Barros
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Cantor
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, CA 94720, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: kuriyan@berkeley.edu.
authors.forename: John
authors.initials: J
authors.lastname: Kuriyan
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D066255:EGF Family of Proteins / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D066255:EGF Family of Proteins; D008024:Ligands; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: allostery; epidermal growth factor receptor; receptor tyrosine kinases; signal transduction