Meta-Biol

• Pathways

The cytoplasmic domain of EGFR contains tyrosine, serine and threonine phosphorylation sites. Dimerization of EGFR activates its intrinsic protein kinase activity and results in autophosphorylation of 6 tyrosine residues in the cytoplasmic tail of EGFR. Tyrosine autophosphorylation is crucial for normal receptor signalling. Five of these tyrosine residues (Y1016 i.e. Y992 in the mature protein, Y1092 i.e. Y1068 in the mature protein, Y1110 i.e. Y1086 in the mature protein, Y1172 i.e. Y1148 in the mature protein and Y1197 i.e. Y1173 in the mature protein ) serve as specific binding sites for cytosolic target proteins involved in signal transmission, while the tyrosine residue Y Y1069 i.e. Y1045 in the mature protein is involved in recruitment of CBL ubiquitin ligase and downregulation of EGFR signaling through degradation of activated EGFR.