荷兰乌特勒支大学Simone Lemeer研究组发现，人类细胞中的组氨酸磷酸化并不具有信号转导功能。相关论文于2022年6月20日在线发表在《自然—方法学》杂志上。

研究人员应用了一个强大的工作流程，其能够明确地检测细菌中的组氨酸磷酸化，并在四个人类细胞系中探测组氨酸磷酸化。最初，在所有研究的人类细胞系中，似乎有数百个蛋白质组氨酸磷酸化被发现。然而，对数据的仔细检查，以及几个对照实验，使研究人员得出结论，这些最初分配的pHis位点中>99%不是真正的，应该是位点定位到邻近的Ser/Thr残基。然而，这个方法有足够的选择性，可以检测到哺乳动物细胞中仅有的几个真正的pHis位点，代表了众所周知酶的中间产物。因此，这些数据中，研究人员没有发现任何证据支持蛋白质组氨酸磷酸化在哺乳动物信号传导中起作用。

据了解，有人认为，在哺乳动物细胞中，蛋白质中的组氨酸残基可能像丝氨酸、苏氨酸和酪氨酸一样频繁地被磷酸化，并可能在哺乳动物的信号传导中发挥关键作用。

附：英文原文

Title: Histidine phosphorylation in human cells; a needle or phantom in the haystack

Author: Leijten, Niels M., Heck, Albert J. R., Lemeer, Simone

Issue&Volume: 2022-06-20

Abstract: It has been suggested that in mammalian cells histidine residues in proteins may become as frequently phosphorylated as serine, threonine and tyrosine, and may play a key role in mammalian signaling. Here we applied a robust workflow that earlier allowed us to detect histidine phosphorylation in bacteria unambiguously, to probe for histidine phosphorylation in four human cell lines. Initially, seemingly hundreds of protein histidine phosphorylations were picked up in all studied human cell lines. However, careful examination of the data, and several control experiments, led us to the conclusion that >99% of these initially assigned pHis sites were not genuine, and should be site localized to neighboring Ser/Thr residues. Nevertheless, our methods are selective enough to detect just a handful of genuine pHis sites in mammalian cells, representing well-known enzymatic intermediates. Consequently, we do not find any evidence in our data supporting that protein histidine phosphorylation plays a role in mammalian signaling. Extensive analyses of mammalian phosphoproteomics datasets show that protein histidine phosphorylation in human cells may not be as prevalent as previously thought.

DOI: 10.1038/s41592-022-01524-0

Source: https://www.nature.com/articles/s41592-022-01524-0