Mechanistic insights into the activation of oncogenic forms of EGF receptor.

摘要: Epidermal growth factor receptor (EGFR) is a tyrosine kinase that commonly activated by mutation in non-small cell lung cancer. The mechanism of this oncogenic activation not completely understood, but contrast to the wild-type EGFR, it proposed be independent domain dimerization. Mechanistic studies on EGFR have mainly relied cell-based assays or isolated measurements. Here we show, using purified, near full-length human proteins (tEGFRs), two mutants are fully active independently EGF and highly resistant therapeutic endogenous inhibitors cetuximab, lapatinib MIG6. Based pattern inhibition effects additional asymmetric dimer interface mutations, propose these drive strongly depend formation for activation, which has implications drug design cancer treatment strategies.