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 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.

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.

scholarly journals Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity

1998 ◽  
Vol 274 (5) ◽  
pp. G863-G870 ◽  
Author(s):  
Adhip P. N. Majumdar ◽  
James R. Goldenring
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Mucosal Cell ◽  
Mucous Cells ◽  
Tyrosine Kinase Activity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mucosal Cell Proliferation

In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether the result of aging or injury or occurring after administration of epidermal growth factor, gastrin, or bombesin, is associated with a rise in tyrosine kinase activity and tyrosine phosphorylation of several mucosal proteins, including a protein with a molecular mass of 53–55 kDa. We hypothesized that this phosphotyrosine membrane protein (referred to as pp55) may play a role in regulating gastric mucosal cell proliferation and differentiation. Purification and subsequent immunoprecipitation studies now show that pp55 is a tyrosine kinase. In addition, the enzyme activity in the gastric mucosa is found to be fourfold higher in aged rats than in young rats. Incubation of gastric mucosal membranes with transforming growth factor-α (2 × 10−8 M) stimulates tyrosine kinase activity of pp55. Immuolocalization studies reveal that pp55 immunoreactivity is predominantly present in mucous cells that are located just above the proliferative zone and spasmolytic peptide-immunoreactive mucous neck cells. Tyrosine kinase activity as well as expression of pp55 are also greatly increased in the gastric mucosa after hypertonic saline-induced injury, a condition that results in stimulation of surface mucosal cell proliferation and differentiation. Our current data suggest that pp55 is a tyrosine kinase, likely localized to pre-surface cells. The presence of pp55 in pre-surface mucous cells and the expression and tyrosine kinase activity of this protein, which can be stimulated during mucosal cell proliferation and differentiation, strongly suggest a role for pp55 in differentiation of gastric surface mucous cells.

scholarly journals The Wnt–NLK Signaling Pathway Inhibits A-Myb Activity by Inhibiting the Association with Coactivator CBP and Methylating Histone H3

2005 ◽  
Vol 16 (10) ◽  
pp. 4705-4713 ◽  
Author(s):  
Toshihiro Kurahashi ◽  
Teruaki Nomura ◽  
Chie Kanei-Ishii ◽  
Yoichi Shinkai ◽  
Shunsuke Ishii
Keyword(s):  
Protein Kinase ◽  
Gene Family ◽  
Family Member ◽  
Kinase Activity ◽  
Histone H3 ◽  
Promoter Regions ◽  
Interacting Protein ◽  
Myb Gene ◽  
Proliferation And Differentiation ◽  
Negative Form

The c-myb proto-oncogene product (c-Myb) regulates proliferation and differentiation of hematopoietic cells. Recently we have shown that c-Myb is degraded in response to Wnt-1 stimulation via a pathway involving TAK1 (TGF-β-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase). NLK and HIPK2 bind directly to c-Myb and phosphorylate c-Myb at multiple sites, inducing its ubiquitination and proteasome-dependent degradation. The mammalian myb gene family contains two members in addition to c-myb, A-myb, and B-myb. Here, we report that the Wnt-NLK pathway also inhibits A-Myb activity, but by a different mechanism. As in the case of c-Myb, both NLK and HIPK2 bound directly to A-Myb and inhibited its activity. NLK phosphorylated A-Myb, but did not induce A-Myb degradation. Overexpression of NLK inhibited the association between A-Myb and the coactivator CBP, thus, blocking A-Myb-induced trans-activation. The kinase activity of NLK is required for the efficient inhibition of the association between A-Myb and CBP, although the kinase-negative form of NLK also partly inhibits the interaction between A-Myb and CBP. Furthermore, NLK induced the methylation of histone H3 at lysine-9 at A-Myb-bound promoter regions. Thus, the Wnt-NLK pathway inhibits the activity of each Myb family member by different mechanisms.

scholarly journals Evidence for Serine/Threonine and Histidine Kinase Activity in the Tobacco Ethylene Receptor Protein NTHK2

2004 ◽  
Vol 136 (2) ◽  
pp. 2971-2981 ◽  
Author(s):  
Zhi-Gang Zhang ◽  
Hua-Lin Zhou ◽  
Tao Chen ◽  
Yan Gong ◽  
Wan-Hong Cao ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Kinase Activity ◽  
Receptor Protein ◽  
Ethylene Receptor

Histidine kinase activity and the regulation of ethylene signal transduction

2005 ◽  
Vol 83 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Michael G Mason ◽  
G Eric Schaller
Keyword(s):  
Signal Transduction ◽  
Plant Growth ◽  
Histidine Kinase ◽  
Kinase Activity ◽  
Ethylene Receptor ◽  
Serine Threonine Kinase ◽  
Two Component ◽  
Ethylene Signal Transduction ◽  
Ethylene Signal

Ethylene is a gaseous hormone that regulates many aspects of plant growth and development. Although the effect of ethylene on plant growth was discovered a century ago, the key players in the ethylene response pathway were only identified over the last 15 years. In Arabidopsis, ethylene is perceived by a family of five receptors (ETR1, ETR2, ERS1, ERS2, and EIN4) that resemble two-component histidine kinases. Of these, only ETR1 and ERS1 contain all the conserved residues required for histidine kinase activity. The ethylene receptors appear to function primarily through CTR1, a serine/threonine kinase that actively suppresses ethylene responses in air (absence of ethylene). Despite recent progress toward understanding ethylene signal transduction, the role of the ethylene-receptor histidine-kinase activity remains unclear. This review considers the significance of histidine kinase activity in ethylene signaling and possible mechanisms by which it may modulate ethylene responses.Key words: ethylene receptor, ETR1, histidine kinase, two-component, phosphorylation, Arabidopsis.

scholarly journals Use of a semisynthetic epitope to probe histidine kinase activity and regulation

2010 ◽  
Vol 397 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Hans K. Carlson ◽  
Lars Plate ◽  
Mark S. Price ◽  
Jasmina J. Allen ◽  
Kevan M. Shokat ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Kinase Activity

scholarly journals CDK6 kinase activity is required for thymocyte development

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6120-6131 ◽  
Author(s):  
Miaofen G. Hu ◽  
Amit Deshpande ◽  
Nicolette Schlichting ◽  
Elisabeth A. Hinds ◽  
Changchuin Mao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Kinase Activity ◽  
Thymocyte Development ◽  
Hematopoietic Stem ◽  
Notch Target Gene ◽  
Target Gene Expression ◽  
Lymphoid Malignancies ◽  
Proliferation And Differentiation

Abstract Cyclin-dependent kinase-6 (CDK6) is required for early thymocyte development and tumorigenesis. To mechanistically dissect the role of CDK6 in thymocyte development, we generated and analyzed mutant knock-in mice and found that mice expressing a kinase-dead Cdk6 allele (Cdk6K43M) had a pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells (Lin−Sca-1+c-Kit+ [LSK]). In contrast, mice expressing the INK4-insensitive, hyperactive Cdk6R31C allele displayed excess proliferation in LSK and thymocytes. However, this is countered at least in part by increased apoptosis, which may limit progenitor and thymocyte expansion in the absence of other genetic events. Our mechanistic studies demonstrate that CDK6 kinase activity contributes to Notch signaling because inactive CDK6 kinase disrupts Notch-dependent survival, proliferation, and differentiation of LSK, with concomitant alteration of Notch target gene expression, such as massive up-regulation of CD25. Further, knockout of CD25 in Cdk6K43M mice rescued most defects observed in young mice. These results illustrate an important role for CDK6 kinase activity in thymocyte development that operates partially through modulating Notch target gene expression. This role of CDK6 as a downstream mediator of Notch identifies CDK6 kinase activity as a potential therapeutic target in human lymphoid malignancies.

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