Kampa D, Burnside J
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19717, USA.
Biochem Biophys Res Commun. 2000 Nov 11;278(1):175-82. doi: 10.1006/bbrc.2000.3757.
Src homology 2 (SH2) domains interact in a highly specific manner with phosphorylated tyrosine residues on other signaling molecules. Protein tyrosine kinases (PTK) frequently contain SH2 domains, which often control signaling specificity. The Janus Kinases (JAKs) are a family of PTKs involved in signal transduction pathways mediated by various cytokines. Initial characterization of JAKs showed no identifiable SH2 domain. However, we have found substantial evidence supporting the existence of an SH2 domain in JAKs through the use of various web-based computational analysis programs. Predictive secondary and tertiary structures recognize an SH2 domain in JAKs. In addition, a three-dimensional homology model was constructed using the SH2 domains of Src tyrosine kinase and Syp tyrosine phosphatase as templates. These results, in conjunction with preliminary binding studies showing interactions with tyrosine phosphorylated proteins in activated splenocytes, suggest a functional role for this domain in JAKs.
Src同源2（SH2）结构域以高度特异性的方式与其他信号分子上的磷酸化酪氨酸残基相互作用。蛋白酪氨酸激酶（PTK）通常含有SH2结构域，其常常控制信号传导特异性。Janus激酶（JAK）是一族参与由各种细胞因子介导的信号转导途径的PTK。对JAK的初步表征未显示可识别的SH2结构域。然而，通过使用各种基于网络的计算分析程序，我们发现了大量证据支持JAK中存在SH2结构域。预测性二级和三级结构识别出JAK中的SH2结构域。此外，以Src酪氨酸激酶和Syp酪氨酸磷酸酶的SH2结构域为模板构建了三维同源模型。这些结果，连同显示活化脾细胞中与酪氨酸磷酸化蛋白相互作用的初步结合研究，提示该结构域在JAK中具有功能作用。
