期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 18, 期 11, 页码 1244-U88出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2135
关键词
-
资金
- 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
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据