Biophysical characterization of recurrent ErbB2 missense mutations reveals alterations in receptor organization and membrane dynamics

• Mutation-dependent ErbB2 activation leads to accelerated ErbB2 diffusion. • EGF/EGFR-induced ErbB2 activation results in restricted lateral diffusion of ErbB2. • Cancer-associated ErbB2 mutations lead to dimerization without phosphorylation. The purpose of this study was to characterize three recurrent, cancer-associated missense mutations in ErbB2, R143Q, R678Q, and V842I, located in the extracellular, juxtamembrane and kinase domains, respectively, to determine how single amino acid substitu