Haendeler J, Berk B C
Center for Cardiovascular Research, University of Rochester, Rochester, NY, USA.
Regul Pept. 2000 Nov 24;95(1-3):1-7. doi: 10.1016/s0167-0115(00)00133-6.
It has been 100 years since the discovery of renin by Bergman and Tigerstedt. Since then, numerous studies have advanced our understanding of the renin-angiotensin system. A remarkable aspect was the discovery that angiotensin II (AngII) is the central product of the renin-angiotensin system and that this octapeptide induces multiple physiological responses in different cell types. In addition to its well known vasoconstrictive effects, growing evidence supports the notion that AngII may play a central role not only in hypertension, but also in cardiovascular and renal diseases. Binding of AngII to the seven-transmembrane angiotensin II type 1 receptor is responsible for nearly all of the physiological actions of AngII. Recent studies underscore the new concept that activation of intracellular second messengers by AngII requires tyrosine phosphorylation. An increasing number of tyrosine kinases have been shown to be activated by AngII, including the Src kinase family, the focal adhesion kinase family, the Janus kinases and receptor tyrosine kinases. These actions of AngII contribute to the pathophysiology of cardiac hypertrophy and remodeling, vascular thickening, heart failure and atherosclerosis. In this review, we discuss the important role of tyrosine kinases in AngII-mediated signal transduction. Understanding the importance of tyrosine phosphorylation in AngII-stimulated signaling events may contribute to new therapies for cardiovascular and renal diseases.
自伯格曼和蒂格斯特德发现肾素以来，已经过去了100年。从那时起，大量研究增进了我们对肾素 - 血管紧张素系统的理解。一个显著的方面是发现血管紧张素II（AngII）是肾素 - 血管紧张素系统的核心产物，并且这种八肽在不同细胞类型中诱导多种生理反应。除了其众所周知的血管收缩作用外，越来越多的证据支持这样一种观点，即AngII不仅在高血压中，而且在心血管和肾脏疾病中可能发挥核心作用。AngII与七跨膜血管紧张素II 1型受体的结合几乎负责了AngII的所有生理作用。最近的研究强调了一个新的概念，即AngII激活细胞内第二信使需要酪氨酸磷酸化。越来越多的酪氨酸激酶已被证明可被AngII激活，包括Src激酶家族、粘着斑激酶家族、Janus激酶和受体酪氨酸激酶。AngII的这些作用促成了心脏肥大和重塑、血管增厚、心力衰竭和动脉粥样硬化的病理生理学。在这篇综述中，我们讨论了酪氨酸激酶在AngII介导的信号转导中的重要作用。了解酪氨酸磷酸化在AngII刺激的信号事件中的重要性可能有助于开发针对心血管和肾脏疾病的新疗法。
