Vetter Stefan W, Zhang Zhong-Yin
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Curr Protein Pept Sci. 2002 Aug;3(4):365-97. doi: 10.2174/1389203023380594.
Protein tyrosine phosphatases, SH2 and PTB domains are crucial elements for cellular signal transduction and regulation. Much effort has been directed towards elucidating their specificity in the past decade using a variety of approaches. Combinatorial library methods have contributed significantly to the understanding of substrate and ligand specificity of phosphoprotein recognizing domains. This review gives a brief overview of the structural characteristics of protein tyrosine phosphatases, SH2 and PTB domains and their binding to phosphopeptides. The chemical synthesis of peptides containing phosphotyrosine or phosphotyrosine mimics and the various formats of synthesis and deconvolution of combinatorial libraries are explained in detail. Examples are given as how different combinatorial libraries have been used to study the interaction of phosphopeptides with SH2 domains and phosphatases. The intrinsic advantages and difficulties of library synthesis, screening and deconvolution are pointed out. Finally, some experimental results on the substrate specificity of protein tyrosine phosphatase 1B and the SH2 domain of the adaptor protein Grb-2 are summarized and discussed.
蛋白质酪氨酸磷酸酶、SH2和PTB结构域是细胞信号转导和调节的关键元件。在过去十年中，人们使用了各种方法致力于阐明它们的特异性。组合文库方法对理解磷蛋白识别结构域的底物和配体特异性做出了重大贡献。本文综述简要概述了蛋白质酪氨酸磷酸酶、SH2和PTB结构域的结构特征及其与磷酸肽的结合。详细解释了含磷酸酪氨酸或磷酸酪氨酸模拟物的肽的化学合成以及组合文库的各种合成和去卷积形式。给出了不同组合文库如何用于研究磷酸肽与SH2结构域和磷酸酶相互作用的实例。指出了文库合成、筛选和去卷积的内在优点和困难。最后，总结并讨论了关于蛋白酪氨酸磷酸酶1B的底物特异性和衔接蛋白Grb-2的SH2结构域的一些实验结果。
