The single transmembrane domains of human receptor tyrosine kinases encode self-interactions

Sci Signal. 2009 Sep 22;2(89):ra56. doi: 10.1126/scisignal.2000547.

Abstract

Transmembrane signaling by receptor tyrosine kinases typically involves a dynamic receptor monomer-dimer equilibrium in which ligand binding to soluble extracellular domains triggers receptor dimerization and subsequent signaling events. Although the role in signal transduction of the single transmembrane helices of individual receptors, which connect the extracellular with the intracellular protein domains, is not understood in detail, we show here that the single transmembrane domains of all 58 human receptor tyrosine kinases alone have an intrinsic propensity to form stable dimeric structures within a membrane. Thus, defined interactions of the transmembrane domains are most likely generally involved in signaling by all human receptor tyrosine kinases.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane / metabolism
  • Dimerization
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Humans
  • In Vitro Techniques
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*

Substances

  • Recombinant Fusion Proteins
  • Receptor Protein-Tyrosine Kinases