EGFR Tyrosine Kinase with Iressa interactions

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EGFR is a transmembrane tyrosine kinase receptor that upon activation with EGF on the extracellular domain, facilitate cell proliferation, survival, motility and differentiation. EGFR forms a homodimer on both the extracellular and cytoplasmic domains. When inactive, the protein forms a symmetric dimer with N lobe to N lobe interactions. However, when activated by EGF and phosphorylation, the protein undergoes conformational changes that form an assymatric dimer with N lobe to C lobe interactions. When active, one of the monomers becomes the receiver for the substrate and ATP, while the other remains the activator. This switches each cycle of the kinase activity. Studies have shown that the mutations, G719S and L858R, are implicated in cancer due to the constitutional activation of the EGFR protein, therefore causing the protein to perpetually activate proliferation. Several drugs are used to inhibit EGFR activity by binding to the ATP-binding cleft, including 4-anilinoquainazolines getfitinib (Iressa).