Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS

摘要: We have used unbiased phosphoproteomic approaches, based on quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture (SILAC), to identify tyrosine phosphorylated proteins isogenic human bronchial epithelial cells (HBECs) and lung adenocarcinoma lines, expressing either of the two mutant alleles EGFR (L858R Del E746-A750), or a KRAS allele, which are common adenocarcinomas. Tyrosine phosphorylation signaling molecules was greater HBECs EGFRs than WT KRAS. Receptor kinases (such as EGFR, ERBB2, MET, IGF1R), Mig-6, an inhibitor signaling, were more RAS. Phosphorylation some differed mutant-expressing cells; for example, junction (β-catenin, plakoglobin, E-cadherin) L858R EGFR. There also differences degree at individual sites within protein; previously uncharacterized site nucleotide-binding loop kinase domains (Y727), ERBB2 (Y735), ERBB4 (Y733), is significantly deletion wild type Signaling not implicated ERBB such polymerase transcript release factor (PTRF), Bayesian network analysis these other datasets revealed that PTRF might be potentially important component network.