EGFR: Activating Mutations and Iressa Inhibition

3D Model

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase protein that dimerises in response to growth factor binding, resulting the activation of the cytoplasmic tyrosine kinase domain. This initiates intracellular signaling pathways for essential cellular processes, including proliferation, differentiation and motility. Mutations resulting in the constituitive activation of EGFR are correlated with the development of non-small cell lung cancers (NSCLCs).

This interactive tour of the EGFR tyrosine kinase domain introduces some of the key interactions involved in the maintainance of the inactive EGFR conformation. It then progresses to depict some common constituitively activating mutations, which are implicated with NSCLCs. Finally, the interactions between Iressa, a competitive inhibitor, and EGFR are discussed, as a means of preventing constituitive EGFR activation.

References: 10.1016/j.ccr.2006.12.017, 10.1074/jbc.M207135200, 10.1158/1535-7163.MCT-12-0880