The epidermal growth factor receptor (EGFR) plays a pivotal role in the development of organisms ranging from worms to humans.Over-expression or aberrant activation of EGFR is also frequently implicated in cancers.The ‘dimerization’ model has long served as a dogma to explain how all the growth factor receptors and others are activated by their ligand.There is,however,accumulating data inconsistent with the model.We therefore studied whether EGFR has a monomeric or dimeric structure on the cell surface by using chemical crosslinking,FRET,sucrose density gradient centrifugation and cysteine disulfide bridge formation.All the results indicate that EGFR has a preformed homo-dimeric structure on the cell surface.We have also studied a molecular mechanism underlying EGFR activation by focusing on the movement of the transmembrane domains during the signaling.