A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling.

摘要: Epidermal growth factor (EGF) and type alpha transforming (TGF-alpha) bind to a specific region in subdomain III of the extracellular portion EGF receptor (EGFR). Binding leads dimerization, auto-and transphosphorylation on intracellular tyrosine residues, activation signal transduction pathways. We compared binding biological actions TGF-alpha Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or variant that has an arginine-to-lysine substitution domain at codon 497 (HER497K) within IV EGFR. Both receptors exhibited two orders sites with radioiodinated (125I-EGF). Similar results were obtained 125I-TGF-alpha HER497R. In contrast, only one order low-affinity was seen case HER497K. Although enhanced phosphorylation both receptors, CHO HER497K attenuated response reduced induction protooncogenes FOS, JUN, MYC. Moreover, high concentrations (5 nM) inhibited these but not These findings indicate regulates across cell membrane selectively modulates characteristics TGF-alpha.