Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins.
Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins.
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表皮生长因子受体与 SH2 结构域蛋白相互作用的结构基础。
DOI：
10.1006/bbrc.1993.1182
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发表时间：
1993
影响因子：
3.1
通讯作者：
Koland,JG
中科院分区：
文献类型：
--
作者：
Sierke,SL;Longo,GM;Koland,JG
研究了激活的表皮生长因子（EGF）受体与SH 2结构域蛋白之间相互作用的结构基础。将c-src SH 2结构域（src同源的第二结构域）表达为重组融合蛋白，并开发了体外测定法来监测EGF受体/SH 2结构域相互作用。在杆状病毒/昆虫细胞系统中表达的EGF受体酪氨酸激酶结构域（TKD）形式显示在磷酸化时与SH 2结构域结合。这些TKD/SH 2结构域相互作用的特征在于解离常数为60-320 nM。缺失分析表明，整个SH 2结构域是识别磷酸化TKD所必需的。高度截短的TKD蛋白与SH 2结构域的结合表明，SH 2结构域识别的位点包括EGF受体自磷酸化位点tyr 992。含有tyr 992的磷酸化EGF受体肽也显示与SH 2结构域相互作用。因此，该残基可能介导src家族中EGF受体和酪氨酸激酶之间的相互作用。
The structural basis of the interactions between the activated epidermal growth factor (EGF) receptor and SH2 domain proteins was investigated. The c-src SH2 domain (second domain of src homology) was expressed as a recombinant fusion protein, and anin vitroassay was developed to monitor EGF receptor/SH2 domain interactions. EGF receptor tyrosine kinase domain (TKD) forms expressed in the baculovirus/insect cell system were shown to bind to the SH2 domain when phosphorylated. These TKD/SH2 domain interactions were characterized by dissociation constants of 60-320 nM. Deletion analysis indicated that the entire SH2 domain was required for recognition of the phosphorylated TKD. The binding of a highly truncated TKD protein to the SH2 domain suggested that the sites recognized by the SH2 domain included the EGF receptor autophosphorylation site, tyr992. A phosphorylated EGF receptor peptide containing tyr992was also shown to interact with the SH2 domain. This residue may therefore mediate interactions between the EGF receptor and tyrosine kinases in the src family.