Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor
Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine-phosphorylated EGF receptor
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DOI：
10.1016/j.jmb.2004.08.072
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发表时间：
2004-10-29
影响因子：
5.6
通讯作者：
He, C
中科院分区：
文献类型：
--
作者：
Zhang, Y;Yan, ZY;He, C
衔接蛋白Doks（酪氨酸激酶的下游）的磷酸酪氨酸结合（PTB）结构域在调节细胞生长、增殖和分化中的细胞表面受体的信号转导中起重要作用;然而，DokPTB结构域的配体特异性迄今为止仍然难以捉摸。在这项研究中，我们研究了Dok 1 PTB结构域和酪氨酸磷酸化EGFR之间特异性关联的分子基础。使用酵母双杂交和生物化学结合试验，我们表明，只有PTB域从Dok 1，而不是Dok 4或Dok 5可以选择性地结合到两个已知的酪氨酸磷酸化位点在Y1086和Y1148在EGFR。我们基于结构的突变分析定义了两个不同的Dok 1 PTB结构域/EGFR相互作用的分子决定因素，并提供了对不同Dok同源物中EGFR和PTB结构域之间特异性相互作用的结构理解。(C)2004爱思唯尔有限公司保留所有权利。
Phosphotyrosine binding (PTB) domains of the adaptor proteins Doks (downstream of tyrosine kinases) play an important role in regulating signal transduction of cell-surface receptors in cell growth, proliferation and differentiation; however, ligand specificity of the Dok PTB domains has until now remained elusive. In this study, we have investigated the molecular basis of specific association between the Dok1 PTB domain and the tyrosine-phosphorylated EGFR. Using yeast two-hybrid and biochemical binding assays, we show that only the PTB domain from Dok1 but not Dok4 or Dok5 can selectively bind to two known tyrosine phosphorylation sites at Y1086 and Y1148 in EGFR. Our structure-based mutational analyses define the molecular determinants for the two distinct Dok1 PTB domain/EGFR interactions and provide the structural understanding of the specific interactions between EGFR and PTB domains in the divergent Dok homologues. (C) 2004 Elsevier Ltd. All rights reserved.