School of Chemistry and Biochemistry, University of Western Australia, Crawley, WA 6009, Australia.
Biochem Soc Trans. 2013 Aug;41(4):1023-8. doi: 10.1042/BST20130019.
It is more than 50 years since protein histidine phosphorylation was first discovered in 1962 by Boyer and co-workers; however, histidine kinases are still much less well recognized than the serine/threonine and tyrosine kinases. The best-known histidine kinases are the two-component signalling kinases that occur in bacteria, fungi and plants. The mechanisms and functions of these kinases, their cognate response regulators and associated phosphorelay proteins are becoming increasingly well understood. When genomes of higher eukaryotes began to be sequenced, it did not appear that they contained two-component histidine kinase system homologues, apart from a couple of related mitochondrial enzymes that were later shown not to function as histidine kinases. However, as a result of the burgeoning sequencing of genomes from a wide variety of eukaryotic organisms, it is clear that there are proteins that correspond to components of the two-component histidine kinase systems in higher eukaryotes and that operational two-component kinase systems are likely to occur in these organisms. There is unequivocal direct evidence that protein histidine phosphorylation does occur in mammals. So far, only nucleoside diphosphate kinases have been shown to be involved in protein histidine phosphorylation, but their mechanisms of action are not well understood. It is clear that other, yet to be identified, histidine kinases also exist in mammals and that protein histidine phosphorylation may play important roles in higher eukaryotes.
自 1962 年 Boyer 及其同事首次发现蛋白质组氨酸磷酸化以来，已经过去了 50 多年；然而，组氨酸激酶的认知程度仍然远低于丝氨酸/苏氨酸和酪氨酸激酶。最著名的组氨酸激酶是存在于细菌、真菌和植物中的双组分信号激酶。这些激酶、它们的同源反应调节剂及其相关磷酸传递蛋白的机制和功能正越来越被人们所理解。当高等真核生物的基因组开始被测序时，除了后来发现不起作用的几个相关的线粒体酶外，似乎并不包含双组分组氨酸激酶系统同源物。然而，由于越来越多的来自各种真核生物的基因组被测序，很明显，在高等真核生物中有与双组分组氨酸激酶系统的组成部分相对应的蛋白质，并且这些生物体中可能存在可操作的双组分激酶系统。有明确的直接证据表明，蛋白质组氨酸磷酸化确实发生在哺乳动物中。到目前为止，只有核苷二磷酸激酶被证明参与了蛋白质组氨酸磷酸化，但它们的作用机制尚不清楚。很明显，其他尚未被识别的组氨酸激酶也存在于哺乳动物中，蛋白质组氨酸磷酸化可能在高等真核生物中发挥重要作用。
