The story of EGFR: from signaling pathways to a potent anticancer target - supplementary material

  

Figure S1: Structure of EGFR 

The EGFR molecule consists of the intracellular and extracellular domains. The extracellular ligand binding domain comprises of four leucine rich subdomains. The transmembrane region is hydrophobic and tethers the receptor to the membrane. The intracellular domain contains a juxtamembrane segment, a tyrosine kinase domain and a C-terminal tail. Upon EGFR activation, phosphorylated c-terminus facilitates protein attachment.

Figure S2: Endocytosis of EGF-bound EGFR.

Endocytic pathway for EGF-EGFR complex degradation and/or recycling. Ligand-bound receptor is internalized by clathrin-dependent or clathrin-independent endocytosis. Internalized ligand and receptor either undergo lysosomal degradation or are recycled back to the plasma membrane. These processes are catalyzed by c-CBL (E3 ubiquitin ligase) and Rab proteins respectively.

Figure S3: Activating Mutations in EGFR Exon 18 – 21 region.

Key mutations in the EGFR exon 18 -21 include deletion mutation at exon 19 - 746ELREA750 (5 bp deletions in codons 746-750), an acquired (secondary) point substitution at exon 20 - T790M (a methionine substituted in place of threonine in codon 790 in the exon 20) and a point substitution at exon 21 - L858R (arginine is substituted for leucine in codon 858 of exon 21).