Signal transduction and oncogenesis by ErbB/HER receptors

Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):903-13. doi: 10.1016/j.ijrobp.2003.06.002.


Growth factors enable cells to escape irradiation-induced death (apoptosis). One important family of growth factors share an epidermal growth factor motif, and all bind to ErbB transmembrane receptors. In response to growth factor ligands, ErbB receptor tyrosine kinases induce a variety of cellular responses, including proliferation, differentiation and motility. Signal transduction pathways are initiated upon ligand-induced receptor homo- or heterodimerization and activation of tyrosine kinase activity. The complement of induced signaling pathways, as well as their magnitude and duration, determines the biological outcome of signaling, and in turn, is regulated by the identity of the ligand and the receptor composition. Recent insights into the structural basis for receptor dimerization, as provided by crystallographic analysis, are described, as is the differential activation of signaling pathways and downregulatory mechanisms. Further, dysregulation of the ErbB network is implicated in a variety of human cancers, and the nature of aberrant signaling through ErbB proteins, as well as current therapeutic approaches, are discussed, highlighting the role of the highly oncogenic ErbB-2 molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Dimerization
  • Down-Regulation
  • Enzyme Activation
  • Ligands
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction / physiology*
  • Structure-Activity Relationship
  • Type C Phospholipases / metabolism


  • Antibodies, Monoclonal
  • Ligands
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • phospholipase C1