Histidine Phosphorylation: Protein Kinases and Phosphatases

被引:4
|
作者
Ning, Jia [1 ]
Sala, Margaux [1 ]
Reina, Jeffrey [1 ]
Kalagiri, Rajasree [1 ]
Hunter, Tony [1 ]
McCullough, Brandon S. [1 ]
机构
[1] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA
关键词
NME; histidine kinase; phosphorylation; histidine phosphatase; NUCLEOSIDE DIPHOSPHATE KINASE; METASTASIS SUPPRESSOR NM23-H1; 14-KDA PHOSPHOHISTIDINE PHOSPHATASE; GENE-EXPRESSION SIGNATURES; LABILE HISTONE PHOSPHATES; HETEROTRIMERIC G-PROTEINS; ATP-CITRATE LYASE; INORGANIC PYROPHOSPHATASE; GASTRIC-CANCER; MESSENGER-RNA;
D O I
10.3390/ijms25147975
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phosphohistidine (pHis) is a reversible protein post-translational modification (PTM) that is currently poorly understood. The P-N bond in pHis is heat and acid-sensitive, making it more challenging to study than the canonical phosphoamino acids pSer, pThr, and pTyr. As advancements in the development of tools to study pHis have been made, the roles of pHis in cells are slowly being revealed. To date, a handful of enzymes responsible for controlling this modification have been identified, including the histidine kinases NME1 and NME2, as well as the phosphohistidine phosphatases PHPT1, LHPP, and PGAM5. These tools have also identified the substrates of these enzymes, granting new insights into previously unknown regulatory mechanisms. Here, we discuss the cellular function of pHis and how it is regulated on known pHis-containing proteins, as well as cellular mechanisms that regulate the activity of the pHis kinases and phosphatases themselves. We further discuss the role of the pHis kinases and phosphatases as potential tumor promoters or suppressors. Finally, we give an overview of various tools and methods currently used to study pHis biology. Given their breadth of functions, unraveling the role of pHis in mammalian systems promises radical new insights into existing and unexplored areas of cell biology.
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页数:41
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