Membrane interaction of bound ligands contributes to the negative binding cooperativity of the EGF receptor.

ABSTRACT: The epidermal growth factor receptor (EGFR) plays a key role in regulating cell proliferation, migration, and differentiation, and aberrant EGFR signaling is implicated in a variety of cancers. EGFR signaling is triggered by extracellular ligand binding, which promotes EGFR dimerization and activation. Ligand-binding measurements are consistent with a negatively cooperative model in which the ligand-binding affinity at either binding site in an EGFR dimer is weaker when the other site is occupied by a ligand. This cooperativity is widely believed to be central to the effects of ligand concentration on EGFR-mediated intracellular signaling. Although the extracellular portion of the human EGFR dimer has been resolved crystallographically, the crystal structures do not reveal the structural o

SUBMITTER: Arkhipov A 

PROVIDER: S-EPMC4109842 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature