Joseph Raji E, Andreotti Amy H
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50010, USA.
Immunol Rev. 2009 Mar;228(1):74-92. doi: 10.1111/j.1600-065X.2008.00740.x.
The control of cellular signaling cascades is of utmost importance in regulating the immune response. Exquisitely precise protein-protein interactions and chemical modification of substrates by enzymatic catalysis are the fundamental components of the signals that alert immune cells to the presence of a foreign antigen. In particular, the phosphorylation events induced by protein kinase activity must be spatially and temporally regulated by specific interactions to maintain a normal and effective immune response. High resolution structures of many protein kinases along with supporting biochemical data are providing significant insight into the intricate regulatory mechanisms responsible for controlling cellular signaling. The Tec family kinases are immunologically important kinases for which regulatory details are beginning to emerge. This review focuses on bringing together structural insights gained over the years to develop an understanding of how domain interactions both within the Tec kinases and between the Tec kinases and other signaling molecules control immune cell function.
细胞信号级联反应的控制在调节免疫反应中至关重要。精确的蛋白质 - 蛋白质相互作用以及酶催化对底物的化学修饰是使免疫细胞警觉外来抗原存在的信号的基本组成部分。特别是,蛋白激酶活性诱导的磷酸化事件必须通过特定相互作用在空间和时间上进行调节,以维持正常且有效的免疫反应。许多蛋白激酶的高分辨率结构以及支持性的生化数据,为深入了解负责控制细胞信号传导的复杂调节机制提供了重要线索。Tec家族激酶是免疫方面重要的激酶,其调节细节正逐渐显现。本综述着重整合多年来获得的结构见解,以深入理解Tec激酶内部以及Tec激酶与其他信号分子之间的结构域相互作用如何控制免疫细胞功能。