EGF signalling amplification induced by dynamic clustering of EGFR
EGF signalling amplification induced by dynamic clustering of EGFR
复制标题
DOI：
10.1016/j.bbrc.2004.09.173
复制
发表时间：
2004-11-19
影响因子：
3.1
通讯作者：
Sako, Y
中科院分区：
文献类型：
--
作者：
Ichinose, J;Murata, M;Sako, Y
侧向相互作用是包括受体酪氨酸激酶(RTK)在内的各种细胞表面受体的重要特征。在这里，我们报告了动态的横向相互作用产生的信号放大和变异的表皮生长因子受体，一个成员的RTK。已知与EGF的结合可诱导EGFR二聚体内的转磷酸化。利用单分子技术，确定了EGF结合和EGFR磷酸化之间的关系。随着未连接的EGFR被磷酸化，磷酸化的EGFR分子的数量变得比结合EGF的分子多，这意味着EGF信号的放大。EGFR形成簇，通过热扩散以及直接和/或间接的横向相互作用不断交换其元素。结果，产生了不同类型的激活受体数量不同的激活位点。扩增不需要细胞质因素，在半完整的细胞上观察到大量的EGFR分子(每个细胞10(4)-10(6)个)，表明这一过程的普遍性。(C)2004 Elsevier Inc.保留所有权利。
Lateral interaction is an important feature of various types of cell surface receptors including the receptor tyrosine kinases (RTKs). Here we report that dynamic lateral interaction produces amplification and variation in signalling of the EGF receptor, a member of RTKs. Binding of EGF is known to induce transphosphorylation inside EGFR dimers. Using single-molecule techniques, the relationship between EGF binding and EGFR phosphorylation has been determined. The number of phosphorylated EGFR molecules became larger than that of EGF binding as unliganded EGFR was phosphorylated, meaning an amplification of EGF signalling. EGFR formed clusters continuously exchanging their elements through thermal diffusion, and direct and/or indirect lateral interactions. As a result, various types of activation sites differing in number of activated receptors were generated. Amplification required no cytoplasmic factors and was observed on semi-intact cells for a wide range of number of EGFR molecules (10(4)-10(6) per cell) suggesting generality of this process. (C) 2004 Elsevier Inc. All rights reserved.