E3375

Sheep Anti-Epidermal Growth Factor Receptor (erbB, EGFR)

Epidermal growth factor (EGF) receptor is a 170kD tyrosine kinase. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling and lysosomal degradation. Phosphorylation of Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the enzyme in an active state and providing a binding surface for substrate proteins. c-Src is involved in phosphorylation of Tyr845. Phospho-tyrosine 992 is a direct binding site for the PLC gamma SH2 domain, resulting in activation of PLC gamma-mediated downstream signaling. Phosphorylation of Tyr1045 creates a major docking site for c-Cbl. Binding of c-Cbl to the activated EGFR leads to receptor ubiquitination and degradation. Phospho-Tyr1068 of activated EGFR is a direct binding site for Grb2. Phospho-tyrosine 1148 and 1173 provide a docking site for SHC. Both sites are involved in the activation of MAP kinase signaling. Phosphorylation of EGFR on serine and threonine residues attenuates EGFR kinase activity. Serines 1046 and 1047 in the carboxy-terminal region of EGFR are sites phosphorylated by CaM kinase II. Mutations to either serine 1046 or 1047 upregulate tyrosine autokinase activity of EGFR.