Signaling of Protein Kinases in Development and Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3729

Special Issue Editor


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Guest Editor
Department of Pharmacology, University of Virginia, Charlottesville, VA, USA
Interests: cell signaling of protein kinases; mechanism of ciliopathy

Special Issue Information

Dear Colleagues,

Protein kinases comprise one of the largest and most abundant gene families in humans and play a pivotal role in signal transduction during tissue development, patterning, and homeostasis through the phosphorylation and functional modulation of protein substrates. Both germ-line and somatic mutations in kinase genes have been associated with many human diseases. Protein kinases are the second most targeted group for drug development. Novel therapeutic strategies to target protein kinases and intervene in cell signaling are still limited due to our incomplete understanding of their signaling mechanisms.

This Special Issue welcomes both comprehensive reviews and original articles to highlight the recent progress in the discovery of new mechanisms by which protein kinases function and human mutations disrupt kinase signaling and impact signal transduction.

Dr. John Zheng Fu
Guest Editor

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Keywords

  • kinase
  • phosphorylation
  • signaling
  • mutation
  • mechanism
  • development
  • inhibitor
  • disease

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Published Papers (3 papers)

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15 pages, 4218 KiB  
Article
A Protein Kinase Cε/Protein Kinase D3 Signalling Axis Modulates RhoA Activity During Cytokinesis
by Ursula Braun and Michael Leitges
Biomedicines 2025, 13(2), 345; https://doi.org/10.3390/biomedicines13020345 - 3 Feb 2025
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Abstract
Background: Protein kinase D3 (PKD3) is a member of the PKD family that has been implicated in many intracellular signalling pathways. However, defined statements regarding PKD isoform specificity and in vivo functions are rare. Methods: Here, we use PKD3-depleted mouse embryonic fibroblast cells [...] Read more.
Background: Protein kinase D3 (PKD3) is a member of the PKD family that has been implicated in many intracellular signalling pathways. However, defined statements regarding PKD isoform specificity and in vivo functions are rare. Methods: Here, we use PKD3-depleted mouse embryonic fibroblast cells and employ various cell culture-based assays and fluorescence microscopy. Results: We show that PKD3 is involved in the regulation of cytokinesis after immortalisation by modulating RhoA activity through a PKCε/PKD3 signalling axis. Conclusions: PKD3 depletion leads to prolonged RhoA activity during cytokinesis, resulting in failed abscission and an increase in the number of multinucleated cells. This identifies a novel, previously unrecognised PKCε/PKD3 pathway involved in the modulation of cytokinesis. Full article
(This article belongs to the Special Issue Signaling of Protein Kinases in Development and Disease)
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14 pages, 2738 KiB  
Article
Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells
by Aline Müller, Maria Lozoya, Xiaoying Chen, Volkmar Weissig and Mahtab Nourbakhsh
Biomedicines 2023, 11(12), 3322; https://doi.org/10.3390/biomedicines11123322 - 15 Dec 2023
Cited by 3 | Viewed by 1843
Abstract
Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential [...] Read more.
Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD. Full article
(This article belongs to the Special Issue Signaling of Protein Kinases in Development and Disease)
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18 pages, 7777 KiB  
Perspective
MAST Kinases’ Function and Regulation: Insights from Structural Modeling and Disease Mutations
by Michael C. Lemke, Nithin R. Avala, Michael T. Rader, Stefan R. Hargett, Daniel S. Lank, Brandon D. Seltzer and Thurl E. Harris
Biomedicines 2025, 13(4), 925; https://doi.org/10.3390/biomedicines13040925 - 9 Apr 2025
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Abstract
Background/Objectives: The MAST kinases are ancient AGC kinases associated with many human diseases, such as cancer, diabetes, and neurodevelopmental disorders. We set out to describe the origins and diversification of MAST kinases from a structural and bioinformatic perspective to inform future research [...] Read more.
Background/Objectives: The MAST kinases are ancient AGC kinases associated with many human diseases, such as cancer, diabetes, and neurodevelopmental disorders. We set out to describe the origins and diversification of MAST kinases from a structural and bioinformatic perspective to inform future research directions. Methods: We investigated MAST-lineage kinases using database and sequence analysis. We also estimate the functional consequences of disease point mutations on protein stability by integrating predictive algorithms and AlphaFold. Results: Higher-order organisms often have multiple MASTs and a single MASTL kinase. MAST proteins conserve an AGC kinase domain, a domain of unknown function 1908 (DUF), and a PDZ binding domain. D. discoideum contains MAST kinase-like proteins that exhibit a characteristic insertion within the T-loop but do not conserve DUF or PDZ domains. While the DUF domain is conserved in plants, the PDZ domain is not. The four mammalian MASTs demonstrate tissue expression heterogeneity by mRNA and protein. MAST1-4 are likely regulated by 14-3-3 proteins based on interactome data and in silico predictions. Comparative ΔΔG estimation identified that MAST1-L232P and G522E mutations are likely destabilizing. Conclusions: We conclude that MAST and MASTL kinases diverged from the primordial MAST, which likely operated in both biological niches. The number of MAST paralogs then expanded to the heterogeneous subfamily seen in mammals that are all likely regulated by 14-3-3 protein interaction. The reported pathogenic mutations in MASTs primarily represent alterations to post-translational modification topology in the DUF and kinase domains. Our report outlines a computational basis for future work in MAST kinase regulation and drug discovery. Full article
(This article belongs to the Special Issue Signaling of Protein Kinases in Development and Disease)
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