Jacobsen Annette V, Murphy James M
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
Biochem Soc Trans. 2017 Jun 15;45(3):665-681. doi: 10.1042/BST20160331.
Over the past decade, our understanding of the mechanisms by which pseudokinases, which comprise ∼10% of the human and mouse kinomes, mediate signal transduction has advanced rapidly with increasing structural, biochemical, cellular and genetic studies. Pseudokinases are the catalytically defective counterparts of conventional, active protein kinases and have been attributed functions as protein interaction domains acting variously as allosteric modulators of conventional protein kinases and other enzymes, as regulators of protein trafficking or localisation, as hubs to nucleate assembly of signalling complexes, and as transmembrane effectors of such functions. Here, by categorising mammalian pseudokinases based on their known functions, we illustrate the mechanistic diversity among these proteins, which can be viewed as a window into understanding the non-catalytic functions that can be exerted by conventional protein kinases.
在过去十年中，随着结构、生化、细胞和遗传学研究的不断增加，我们对假激酶（其在人类和小鼠激酶组中约占10%）介导信号转导机制的理解有了迅速进展。假激酶是传统活性蛋白激酶的催化缺陷对应物，已被赋予多种功能，如作为蛋白相互作用结构域，充当传统蛋白激酶和其他酶的变构调节剂、蛋白运输或定位的调节剂、信号复合物组装成核的枢纽以及此类功能的跨膜效应器。在这里，通过根据已知功能对哺乳动物假激酶进行分类，我们展示了这些蛋白质之间的机制多样性，这可以被视为了解传统蛋白激酶可能发挥的非催化功能的一个窗口。
