Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 18, Issue 11, Pages 1244-U88Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2135
Keywords
-
Funding
- National Science Foundation [CAREER MCB-0845062]
- Oxnard Foundation
- US National Institutes of Health (NIH) [R21RR024438]
- NIH [R01CA119232]
- National Science Foundation
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0845062] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Physics [0954836] Funding Source: National Science Foundation
Ask authors/readers for more resources
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 dimerize. Blockade of erbB1 kinase activity or disruption of actin networks results in faster diffusion of receptor dimers. These results implicate both signal propagation and the cortical cytoskeleton in reduced mobility of signaling-competent erbB1 dimers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available