The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency.

摘要: Although activation of the ErbB family receptor tyrosine kinases (ErbB1-4) is driven by oligomerization mediated intermolecular interactions between extracellular, kinase and transmembrane domains, domain has been largely neglected in this regard. The largest contributor to intramembrane electric field, dipole potential, alters conformation peptides, but its effect on proteins unknown. Here, we show Forster resonance energy transfer (FRET) number brightness (N&B) experiments that epidermal growth factor (EGF)-induced increase homoassociation ErbB1 ErbB2 their heteroassociation are augmented increasing potential. These effects were even more pronounced for harboring an activating Val → Glu mutation (NeuT). signaling capacity was also correlated with Since potential decreased affinity EGF ErbB1, factor-induced at elevated actually induced lower occupancy. We conclude plays a permissive role clustering receptors lipid rafts ligand binding can be partially attributed