He Lijuan, Hristova Kalina
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Biochim Biophys Acta. 2012 Apr;1818(4):995-1005. doi: 10.1016/j.bbamem.2011.07.044. Epub 2011 Aug 5.
RTKs, the second largest family of membrane receptors, exert control over cell proliferation, differentiation and migration. In recent years, our understanding of RTK structure and activation in health and disease has skyrocketed. Here we describe experimental approaches used to interrogate RTKs, and we review the quantitative biophysical frameworks and structural considerations that shape our understanding of RTK function. We discuss current knowledge about RTK interactions, focusing on the role of different domains in RTK homodimerization, and on the importance and challenges in RTK heterodimerization studies. We also review our understanding of pathogenic RTK mutations, and the underlying physical-chemical causes for the pathologies. This article is part of a Special Issue entitled: Protein Folding in Membranes.
受体酪氨酸激酶(RTKs)是第二大膜受体家族,对细胞增殖、分化和迁移发挥调控作用。近年来,我们对RTK在健康和疾病状态下的结构及激活机制的理解有了飞速提升。在此,我们描述用于研究RTK的实验方法,并回顾形成我们对RTK功能理解的定量生物物理框架和结构考量因素。我们讨论关于RTK相互作用的现有知识,重点关注不同结构域在RTK同源二聚化中的作用,以及RTK异源二聚化研究的重要性和挑战。我们还回顾了对致病性RTK突变的理解,以及这些病变背后的物理化学原因。本文是名为《膜蛋白折叠》特刊的一部分。