ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding.
ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding.
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DOI：
10.1038/nsmb.2135
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发表时间：
2011-10-23
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
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配体占据和二聚化对erbB 1信号传导的贡献程度存在争议。为了检验这一点，我们利用双色量子点跟踪来可视化erbB1同源二聚化和定量活细胞上的二聚体解离速率（koff）。使用3状态隐马尔可夫模型提取动力学参数，以确定自由、共约束和二聚化状态之间的转换速率。我们报告说，二聚体组成的2配体结合受体是长寿和他们的koff是独立的激酶活性。相比之下，未配体的二聚体具有>4倍更快的koff。受体的瞬时共限制促进重复相遇并增强二聚体形成。当配体结合受体二聚化时，迁移率降低>6倍。阻断erbB1激酶活性或破坏肌动蛋白网络导致受体二聚体扩散加快。这些结果暗示信号传播和皮质细胞骨架的信号能力erbB1二聚体的流动性降低。
The extent to which ligand occupancy and dimerization contribute to erbB1 signaling is controversial. To examine this, we utilized two-color Quantum Dot tracking for visualization of erbB1 homodimerization and quantification of the dimer off rate (koff) on living cells. Kinetic parameters were extracted using a 3-state Hidden Markov Model to identify transition rates between free, co-confined, and dimerized states. We report that dimers composed of 2 ligand-bound receptors are long-lived and their koff is independent of kinase activity. By comparison, unliganded dimers have >4-fold faster koff. Transient co-confinement of receptors promotes repeated encounters and enhances dimer formation. Mobility decreases >6-fold 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.
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DOI：
10.1083/jcb.200503140
发表时间：
2005-08-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lidke DS;Lidke KA;Rieger B;Jovin TM;Arndt-Jovin DJ
通讯作者：
Arndt-Jovin DJ
影响因子：
46.9
作者：
Lidke, DS;Nagy, P;Jovin, TM
通讯作者：
Jovin, TM
影响因子：
3.4
作者：
Chen, Lirong;Merzlyakov, Mikhail;Hristova, Kalina
通讯作者：
Hristova, Kalina
DOI：
10.1016/j.bbrc.2004.09.173
发表时间：
2004-11-19
影响因子：
3.1
作者：
Ichinose, J;Murata, M;Sako, Y
通讯作者：
Sako, Y
影响因子：
11.4
作者：
Lemmon, MA;Bu, ZM;Schlessinger, J
通讯作者：
Schlessinger, J