SH2 domains: role, structure and implications for molecular medicine.
SH2 domains: role, structure and implications for molecular medicine.
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SH2 域：分子医学的作用、结构和影响。
DOI：
10.1017/s1462399404007331
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发表时间：
2004
影响因子：
6.2
通讯作者：
Lubman,Olga
中科院分区：
文献类型：
--
作者：
Waksman,Gabriel;Kumaran,Sangaralingam;Lubman,Olga
Src同源2（SH2）结构域是在参与酪氨酸激酶信号级联的许多蛋白质中发现的蛋白质模块（约100个氨基酸）。它们的功能是结合特定蛋白质靶标中的酪氨酸磷酸化序列。SH2结构域与其同源酪氨酸磷酸化靶的结合将受体活化与下游信号传导连接，既连接到细胞核以调节基因表达，又连接到整个细胞的细胞质。本文综述了SH2结构域在正常和疾病状态下发挥的作用，描述了SH2结构域研究在破译其作用机制方面的成功，并概述了使用SH2结构域作为抑制剂药物设计的结构模板。
Src homology 2 (SH2) domains are protein modules (of ~100 amino acids) found in many proteins involved in tyrosine kinase signalling cascades. Their function is to bind tyrosine-phosphorylated sequences in specific protein targets. Binding of an SH2 domain to its cognate tyrosine-phosphorylated target links receptor activation to downstream signalling, both to the nucleus to regulate gene expression and throughout the cytoplasm of the cell. This review recapitulates the roles that SH2 domains play in normal and diseased states, describes the successes of SH2 domain research in deciphering their mechanism of action, and provides an overview of the use of SH2 domains as structural templates for the design of inhibitor drugs.