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Histidine Phosphorylation: Protein Kinases and Phosphatases

Authors :
Jia Ning
Margaux Sala
Jeffrey Reina
Rajasree Kalagiri
Tony Hunter
Brandon S. McCullough
Source :
International Journal of Molecular Sciences, Vol 25, Iss 14, p 7975 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
25
Issue :
14
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.f83249d9f5de442fa66e6b5108ce86e6
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms25147975