Department of Cardiovascular Science, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.
Biochem Soc Trans. 2011 Apr;39(2):684-7. doi: 10.1042/BST0390684.
Sensing and interpreting extracellular signals in response to changes in the environment has been a fundamental feature of all life forms from the very beginning of evolution. To fulfil this function, networks of proteins have evolved, forming the intracellular signal transduction machinery. Whereas the appropriate control of these signal transduction systems is essential to homoeostasis, dysregulation of signalling leads to disease and often the death of the organism. The tribbles family of pseudokinases have emerged in recent years as key controllers of signal transduction via their interactions with several key kinases, ubiquitin ligases and transcription factors. In line with their role in regulating fundamentally important signalling pathways, members of the tribbles family have been implicated in the development of a range of human diseases. Whereas our mechanistic understanding of how these proteins contribute to disease is far from complete, the present paper attempts to summarize some of the most important recent developments in this field of research.
从进化的一开始，感应和解释细胞外信号以响应环境变化一直是所有生命形式的基本特征。为了履行这一功能，蛋白质网络已经进化，形成了细胞内信号转导机制。虽然这些信号转导系统的适当控制对于体内平衡至关重要，但信号的失调会导致疾病，并且常常导致生物体的死亡。近年来，tribbles 家族的拟激酶作为关键的信号转导控制器而出现，它们通过与几种关键激酶、泛素连接酶和转录因子相互作用来实现这一功能。与它们在调节基本重要的信号通路中的作用一致，tribbles 家族的成员与一系列人类疾病的发生有关。尽管我们对这些蛋白质如何导致疾病的机制理解还远远不够，但本文试图总结这一研究领域的一些最重要的最新进展。
