scholarly journals NME/NM23/NDPK and Histidine Phosphorylation

2020 ◽  
Vol 21 (16) ◽  
pp. 5848
Author(s):  
Kevin Adam ◽  
Jia Ning ◽  
Jeffrey Reina ◽  
Tony Hunter
Keyword(s):  
Histidine Kinase ◽  
Kinase Activity ◽  
Current Knowledge ◽  
Family Members ◽  
Nucleoside Diphosphate Kinase ◽  
Molecular Tools ◽  
New Methods ◽  
Functional Aspects ◽  
Histidine Phosphorylation ◽  
Nucleoside Diphosphate Kinases

The NME (Non-metastatic) family members, also known as NDPKs (nucleoside diphosphate kinases), were originally identified and studied for their nucleoside diphosphate kinase activities. This family of kinases is extremely well conserved through evolution, being found in prokaryotes and eukaryotes, but also diverges enough to create a range of complexity, with homologous members having distinct functions in cells. In addition to nucleoside diphosphate kinase activity, some family members are reported to possess protein-histidine kinase activity, which, because of the lability of phosphohistidine, has been difficult to study due to the experimental challenges and lack of molecular tools. However, over the past few years, new methods to investigate this unstable modification and histidine kinase activity have been reported and scientific interest in this area is growing rapidly. This review presents a global overview of our current knowledge of the NME family and histidine phosphorylation, highlighting the underappreciated protein-histidine kinase activity of NME family members, specifically in human cells. In parallel, information about the structural and functional aspects of the NME family, and the knowns and unknowns of histidine kinase involvement in cell signaling are summarized.

Histidine kinases from bacteria to humans

2013 ◽  
Vol 41 (4) ◽  
pp. 1023-1028 ◽  
Author(s):  
Paul V. Attwood
Keyword(s):  
Histidine Kinase ◽  
Tyrosine Kinases ◽  
Mitochondrial Enzymes ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Two Component ◽  
Higher Eukaryotes ◽  
Histidine Phosphorylation ◽  
Eukaryotic Organisms ◽  
Nucleoside Diphosphate Kinases

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.

scholarly journals The Potential Functional Roles of NME1 Histidine Kinase Activity in Neuroblastoma Pathogenesis

2020 ◽  
Vol 21 (9) ◽  
pp. 3319 ◽  
Author(s):  
Kevin Adam ◽  
Jacqueline Lesperance ◽  
Tony Hunter ◽  
Peter E. Zage
Keyword(s):  
Cell Migration ◽  
Histidine Kinase ◽  
Kinase Activity ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Functional Roles ◽  
Patient Prognosis ◽  
Histidine Phosphorylation ◽  
Tumor In Childhood ◽  
Neuroblastoma Cell Lines

Neuroblastoma is the most common extracranial solid tumor in childhood. Gain of chromosome 17q material is found in >60% of neuroblastoma tumors and is associated with poor patient prognosis. The NME1 gene is located in the 17q21.3 region, and high NME1 expression is correlated with poor neuroblastoma patient outcomes. However, the functional roles and signaling activity of NME1 in neuroblastoma cells and tumors are unknown. NME1 and NME2 have been shown to possess histidine (His) kinase activity. Using anti-1- and 3-pHis specific monoclonal antibodies and polyclonal anti-pH118 NME1/2 antibodies, we demonstrated the presence of pH118-NME1/2 and multiple additional pHis-containing proteins in all tested neuroblastoma cell lines and in xenograft neuroblastoma tumors, supporting the presence of histidine kinase activity in neuroblastoma cells and demonstrating the potential significance of histidine kinase signaling in neuroblastoma pathogenesis. We have also demonstrated associations between NME1 expression and neuroblastoma cell migration and differentiation. Our demonstration of NME1 histidine phosphorylation in neuroblastoma and of the potential role of NME1 in neuroblastoma cell migration and differentiation suggest a functional role for NME1 in neuroblastoma pathogenesis and open the possibility of identifying new therapeutic targets and developing novel approaches to neuroblastoma therapy.

Histone H4 histidine phosphorylation: kinases, phosphatases, liver regeneration and cancer

2012 ◽  
Vol 40 (1) ◽  
pp. 290-293 ◽  
Author(s):  
Paul G. Besant ◽  
Paul V. Attwood
Keyword(s):  
Histidine Kinase ◽  
Kinase Activity ◽  
Mechanical Damage ◽  
Hepatocyte Proliferation ◽  
Histone H4 ◽  
Proliferation And Differentiation ◽  
Histidine Phosphorylation ◽  
Proliferation Of Hepatocytes ◽  
Hepatocellular Carcinoma Tissue ◽  
Human Foetal Liver

Phosphorylation of histone H4 on one or both of its two histidine residues has been known to occur in liver cells for nearly 40 years and has been associated with proliferation of hepatocytes during regeneration of the liver following mechanical damage. More recently, large increases in histone H4 histidine kinase activity have been found to occur associated with proliferation and differentiation of liver progenitor cells following chemical damage that prevents hepatocyte proliferation. In addition, it has been shown this histone H4 histidine kinase activity is elevated nearly 100-fold in human foetal liver and several hundredfold in hepatocellular carcinoma tissue compared with normal adult liver. In the present paper, we review what is currently known about histone H4 histidine phosphorylation, the kinase(s) responsible and the phosphatases capable of catalysing its dephosphorylation, and briefly summarize the techniques used to detect and measure the histidine phosphorylation of histone H4 and the corresponding kinase activity.

scholarly journals Glycosylation of matrix metalloproteases and tissue inhibitors: present state, challenges and opportunities

2016 ◽  
Vol 473 (11) ◽  
pp. 1471-1482 ◽  
Author(s):  
Lise Boon ◽  
Estefania Ugarte-Berzal ◽  
Jennifer Vandooren ◽  
Ghislain Opdenakker
Keyword(s):  
Matrix Metalloproteinases ◽  
Present State ◽  
Cellular Localization ◽  
Current Knowledge ◽  
Matrix Metalloproteases ◽  
Inhibitor Binding ◽  
Attachment Sites ◽  
Functional Aspects ◽  
Functional Implications ◽  
Challenges And Opportunities

Current knowledge about the glycosylation of matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) is reviewed. Whereas structural and functional aspects of the glycobiology of many MMPs is unknown, research on MMP-9 and MMP-14 glycosylation reveals important functional implications, such as altered inhibitor binding and cellular localization. This, together with the fact that MMPs contain conserved and many potential attachment sites for N-linked and O-linked oligosaccharides, proves the need for further studies on MMP glycobiology.

scholarly journals Dangerous Duplicity: The Dual Functions of Casein Kinase 1in Parasite Biology and Host Subversion

2021 ◽  
Vol 11 ◽  
Author(s):  
Najma Rachidi ◽  
Uwe Knippschild ◽  
Gerald F. Späth
Keyword(s):  
Current Knowledge ◽  
Family Members ◽  
Casein Kinase ◽  
Biological Processes ◽  
Casein Kinase 1 ◽  
Parasite Survival ◽  
Host Pathogen ◽  
Parasite Biology ◽  
Antimicrobial Interventions

Casein Kinase 1 (CK1) family members are serine/threonine protein kinases that are involved in many biological processes and highly conserved in eukaryotes from protozoan to humans. Even though pathogens exploit host CK1 signaling pathways to survive, the role of CK1 in infectious diseases and host/pathogen interaction is less well characterized compared to other diseases, such as cancer or neurodegenerative diseases. Here we present the current knowledge on CK1 in protozoan parasites highlighting their essential role for parasite survival and their importance for host-pathogen interactions. We also discuss how the dual requirement of CK1 family members for parasite biological processes and host subversion could be exploited to identify novel antimicrobial interventions.

scholarly journals 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias

2020 ◽  
Vol 59 (1) ◽  
pp. 145-298 ◽  
Author(s):  
Edmond M. Cronin ◽  
Frank M. Bogun ◽  
Philippe Maury ◽  
Petr Peichl ◽  
Minglong Chen ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Ventricular Arrhythmias ◽  
Cardiac Electrophysiology ◽  
Current Knowledge ◽  
Meta Analysis ◽  
Expert Consensus ◽  
New Methods ◽  
Writing Group ◽  
Knowledge And Practice

Abstract Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.

Defective protein histidine phosphorylation in islets from the Goto-Kakizaki diabetic rat

2003 ◽  
Vol 285 (3) ◽  
pp. E498-E503 ◽  
Author(s):  
Anjaneyulu Kowluru
Keyword(s):  
G Proteins ◽  
Nucleoside Diphosphate Kinase ◽  
Diabetic Rat ◽  
Β Cells ◽  
Gk Rat ◽  
Β Cell ◽  
Histidine Kinases ◽  
Insulin Dependent ◽  
Endogenous Proteins ◽  
Histidine Phosphorylation

We recently described novel regulatory roles for protein histidine phosphorylation of key islet proteins (e.g., nucleoside diphosphate kinase and succinyl thiokinase) in insulin secretion from the islet β-cell (Kowluru A. Diabetologia 44: 89-94, 2001; Kowluru A, Tannous M, and Chen HQ. Arch Biochem Biophys 398: 160-169, 2002). In this context, we also characterized a novel, ATP- and GTP-sensitive protein histidine kinase in isolated β-cells that catalyzed the histidine phosphorylation of islet (endogenous) proteins as well as exogenously added histone 4, and we implicated this kinase in the activation of islet endogenous G proteins (Kowluru A. Biochem Pharmacol 63: 2091-2100, 2002). In the present study, we describe abnormalities in ATP- or GTP-mediated histidine phosphorylation of nucleoside diphosphate kinase in islets derived from the Goto-Kakizaki (GK) rat, a model for non-insulin-dependent diabetes. Furthermore, we provide evidence for a marked reduction in the activities of ATP- or GTP-sensitive histidine kinases in GK rat islets. On the basis of these observations, we propose that alterations in protein histidine phosphorylation could contribute toward insulin-secretory abnormalities demonstrable in the diabetic islet.

scholarly journals FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

2019 ◽  
Vol 99 (3) ◽  
pp. 1433-1466 ◽  
Author(s):  
Julhash U. Kazi ◽  
Lars Rönnstrand
Keyword(s):  
Signal Transduction ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Biological Effects ◽  
Acquired Resistance ◽  
Cell Proliferation And Differentiation ◽  
Functional Aspects ◽  
Proliferation And Differentiation ◽  
Targeted Inhibition

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is expressed almost exclusively in the hematopoietic compartment. Its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. Activation of FLT3 leads to its autophosphorylation and initiation of several signal transduction cascades. Signaling is initiated by the recruitment of signal transduction molecules to activated FLT3 through binding to specific phosphorylated tyrosine residues in the intracellular region of FLT3. Activation of FLT3 mediates cell survival, cell proliferation, and differentiation of hematopoietic progenitor cells. It acts in synergy with several other cytokines to promote its biological effects. Deregulated FLT3 activity has been implicated in several diseases, most prominently in acute myeloid leukemia where around one-third of patients carry an activating mutant of FLT3 which drives the disease and is correlated with poor prognosis. Overactivity of FLT3 has also been implicated in autoimmune diseases, such as rheumatoid arthritis. The observation that gain-of-function mutations of FLT3 can promote leukemogenesis has stimulated the development of inhibitors that target this receptor. Many of these are in clinical trials, and some have been approved for clinical use. However, problems with acquired resistance to these inhibitors are common and, furthermore, only a fraction of patients respond to these selective treatments. This review provides a summary of our current knowledge regarding structural and functional aspects of FLT3 signaling, both under normal and pathological conditions, and discusses challenges for the future regarding the use of targeted inhibition of these pathways for the treatment of patients.

scholarly journals Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shekhar Srivastava ◽  
Saswati Panda ◽  
Zhai Li ◽  
Stephen R Fuhs ◽  
Tony Hunter ◽  
...  
Keyword(s):  
Potassium Channel ◽  
T Cell Activation ◽  
Cell Activation ◽  
Phosphorylation Site ◽  
Nucleoside Diphosphate Kinase ◽  
Calcium Flux ◽  
Channel Activity ◽  
Nucleoside Diphosphate Kinase B ◽  
Regulatory Phosphorylation ◽  
Histidine Phosphorylation

KCa2.1, KCa2.2, KCa2.3 and KCa3.1 constitute a family of mammalian small- to intermediate-conductance potassium channels that are activated by calcium-calmodulin. KCa3.1 is unique among these four channels in that activation requires, in addition to calcium, phosphorylation of a single histidine residue (His358) in the cytoplasmic region, by nucleoside diphosphate kinase-B (NDPK-B). The mechanism by which KCa3.1 is activated by histidine phosphorylation is unknown. Histidine phosphorylation is well characterized in prokaryotes but poorly understood in eukaryotes. Here, we demonstrate that phosphorylation of His358 activates KCa3.1 by antagonizing copper-mediated inhibition of the channel. Furthermore, we show that activated CD4+ T cells deficient in intracellular copper exhibit increased KCa3.1 histidine phosphorylation and channel activity, leading to increased calcium flux and cytokine production. These findings reveal a novel regulatory mechanism for a mammalian potassium channel and for T-cell activation, and highlight a unique feature of histidine versus serine/threonine and tyrosine as a regulatory phosphorylation site.

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