Epidermal Growth Factor-related Peptides Activate Distinct Subsets of ErbB Receptors and Differ in Their Biological Activities

摘要: Numerous epidermal growth factor (EGF)-related peptide binding members of the ErbB family receptor tyrosine kinases have been described. While several EGF agonists bind and activate ErbB-1/EGF receptor, neu differentiation (NDF) functions as a ligand for ErbB-3 ErbB-4. However, it is currently unknown which specific subsets receptors become activated in response to each these ligands. The present study addresses this issue using T47D breast tumor cell line, expresses moderate levels all presently known receptors. We show that agonists, but not NDF, stimulated phosphorylation ErbB-1. In contrast, EGF-related factors except amphiregulin were able induce ErbB-2. ability varied dramatically among different peptides. EGF, transforming (TGF)-alpha, only had effect, NDF increased phosphotyrosine content. Most notably, heparin (HB-EGF) betacellulin (BTC) more effective than other agonists. Consequently, HB-EGF, BTC significantly association phosphatidylinositol kinase activity with ErbB-3. Among HB-EGF induced low level ErbB-4 phosphorylation, while was efficient activating activation appears be independent ErbB-1, shown by pretreatment cells an antibody inhibits As result differential receptors, most distinguishable biological activities on cultured mammary epithelial lines.