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Protein Kinases in Neurological Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 860

Special Issue Editor


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Guest Editor
Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA 94305, USA
Interests: kinases; cell signalling; cryoEM; crystallography; virology; neurological disorder

Special Issue Information

Dear Colleagues,

Protein kinases are a class of phosphotransferases that phosphorylate proteins by transferring the gamma-phosphoryl group of ATP to specific amino acid residues of the substrate. The kinase family of proteins help regulate important physiological processes in inflammation, metabolism and immunity. Kinases are essential cell signaling molecules known to be involved in neurological disorders.

Although protein kinases have been an important research topic in the field of life medicine, the role of protein kinases within the nervous system is far from being fully understood. By combining conventional routes of molecular biology with advanced technologies, such as those in proteomics, imaging and structural biology, we can further explore the extensive roles of protein kinases within neural processes. These discoveries will help in the continuous effort toward improving treatment for neurodegenerative disorders and other neurological conditions.

We are assembling a Special Issue focusing on the relationship between kinases and human neurological disorders. We welcome all submission types on this topic.

Dr. Valerie L. Tokars
Guest Editor

Manuscript Submission Information

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Keywords

  • kinases
  • neurological disorder
  • health
  • signaling
  • neuropsychiatric

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Published Papers (1 paper)

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Research

16 pages, 2861 KiB  
Article
Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation
by Aditya K. Singh, Jully Singh, Nana A. Goode and Fernanda Laezza
Int. J. Mol. Sci. 2024, 25(15), 8069; https://doi.org/10.3390/ijms25158069 - 24 Jul 2024
Viewed by 623
Abstract
The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). [...] Read more.
The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 kinase pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce the FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on the FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (INa) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak INa density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitor’s opposite effects on INa. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine, and GSK3 inhibitor XIII was also observed in long-term inactivation and use dependency of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome. Full article
(This article belongs to the Special Issue Protein Kinases in Neurological Disorders)
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