Hubbard S R, Till J H
Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Annu Rev Biochem. 2000;69:373-98. doi: 10.1146/annurev.biochem.69.1.373.
Tyrosine phosphorylation is one of the key covalent modifications that occurs in multicellular organisms as a result of intercellular communication during embryogenesis and maintenance of adult tissues. The enzymes that carry out this modification are the protein tyrosine kinases (PTKs), which catalyze the transfer of the phosphate of ATP to tyrosine residues on protein substrates. Phosphorylation of tyrosine residues modulates enzymatic activity and creates binding sites for the recruitment of downstream signaling proteins. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs. Because PTKs are critical components of cellular signaling pathways, their catalytic activity is strictly regulated. Over the past several years, high-resolution structural studies of PTKs have provided a molecular basis for understanding the mechanisms by which receptor and nonreceptor PTKs are regulated. This review will highlight the important results that have emerged from these structural studies.
酪氨酸磷酸化是多细胞生物中发生的关键共价修饰之一，它是胚胎发育和成年组织维持过程中细胞间通讯的结果。进行这种修饰的酶是蛋白酪氨酸激酶（PTK），它催化将ATP的磷酸基团转移到蛋白质底物上的酪氨酸残基上。酪氨酸残基的磷酸化调节酶活性，并为下游信号蛋白的募集创造结合位点。细胞中存在两类PTK：跨膜受体PTK和非受体PTK。由于PTK是细胞信号通路的关键组成部分，它们的催化活性受到严格调控。在过去几年中，PTK的高分辨率结构研究为理解受体和非受体PTK的调控机制提供了分子基础。本综述将重点介绍这些结构研究中出现的重要结果。
