Spatial control of EGF receptor activation by reversible dimerization on living cells

Here, the dimerization dynamics of individual epidermal growth factor receptor (EGFR) molecules have been determined in living cells in real time using a quantum-dot-based approach. Signalling by EGFR, a type I receptor kinase that has been implicated in a number if human carcinomas, is preceded by receptor dimerization. It has been widely assumed that ligand binding is required to trigger conformation changes in EGFR, which in turn lead to dimer formation and kinase activation. However, this new work shows that dimerization is a continuous and reversible process, with ligand binding serving to stabilize receptor dimers by decreasing their rate of dissociation, thereby increasing the stable dimer population in a given cell. In addition, the location of the receptor is important, with spontaneous dimer formation being more prevalent at the cell margins than at the cell centre.