The ErbB kinase domain: Structural perspectives into kinase activation and inhibition

Ron Bose, Xuewu Zhang

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations


Epidermal growth factor receptor (EGFR) and its family members, ErbB2, ErbB3 and ErbB4, are receptor tyrosine kinases which send signals into the cell to regulate many critical processes including development, tissue homeostasis, and tumorigenesis. Central to the signaling of these receptors is their intracellular kinase domain, which is activated by ligand-induced dimerization of the receptor and phosphorylates several tyrosine residues in the C-terminal tail. The phosphorylated tail then recruits other signaling molecules and relays the signal to downstream pathways. A model of the autoinhibition, activation and feedback inhibition mechanisms for the ErbB kinase domain has emerged from a number of recent structural studies. Meanwhile, recent clinical studies have revealed the relationship between specific ErbB kinase mutations and the responsiveness to kinase inhibitor drugs.We will review these regulation mechanisms of the ErbB kinase domain, and discuss the binding specificity of kinase inhibitors and the effects of kinase domain mutations found in cancer patients from a structural perspective.

Original languageEnglish (US)
Pages (from-to)649-658
Number of pages10
JournalExperimental Cell Research
Issue number4
StatePublished - Feb 15 2009


  • Activation loop
  • Epidermal growth factor receptor
  • Growth factor receptor
  • Lung cancer
  • MIG6
  • Receptor dimerization
  • Receptor tyrosine kinase
  • Signal transduction
  • Structural biology
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cell Biology


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