The EGF receptor family: spearheading a merger of signaling and therapeutics

Curr Opin Cell Biol. 2007 Apr;19(2):124-34. doi: 10.1016/ Epub 2007 Feb 20.


The ErbB receptor tyrosine kinases evolved as key regulatory entities enabling the extracellular milieu to communicate with the intracellular machinery to bring forth the appropriate biological response in an ever-changing environment. Since its discovery, many aspects of the ErbB family have been deciphered, with emphasis on aberration of signaling in human diseases. However, only now, with the availability of the atomic coordinates of these receptors, can we construct a comprehensive model of the mechanisms underlying ligand-induced receptor dimerization and subsequent tyrosine kinase activation. Furthermore, the recent introduction of new high-throughput screening methodologies, combined with the materialization of a systems biology perspective, reveals an overwhelming network complexity, enabling robust signaling and evolvability. This knowledge is likely to impact our view of diseases as system perturbations and resistance to ErbB-targeted therapeutics as manifestations of robustness.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Animals
  • Computer Simulation
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism*
  • Humans
  • Ligands
  • Models, Biological
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neuregulins / metabolism
  • Protein Conformation
  • Signal Transduction*


  • Ligands
  • Neuregulins
  • ErbB Receptors