ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding.

ABSTRACT: The extent to which ligand occupancy and dimerization contribute to erbB1 signaling is controversial. To examine this, we used two-color quantum-dot tracking for visualization of the homodimerization of human erbB1 and quantification of the dimer off-rate (k(off)) on living cells. Kinetic parameters were extracted using a three-state hidden Markov model to identify transition rates between free, co-confined and dimerized states. We report that dimers composed of two ligand-bound receptors are long-lived and their k(off) is independent of kinase activity. By comparison, unliganded dimers have a more than four times faster k(off). Transient co-confinement of receptors promotes repeated encounters and enhances dimer formation. Mobility decreases more than six times when ligand-bound receptors

SUBMITTER: Low-Nam ST 

PROVIDER: S-EPMC3210321 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature