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Protein Kinase in Disease, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 July 2025 | Viewed by 707

Special Issue Editor


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Guest Editor
Disease Biomarker Analysis and Molecular Regulation, Graduate School of Medicine, St Marianna University, Miyamae Ku, 2-16-1 Sugao, Kawasaki 2168511, Kanagawa, Japan
Interests: protein kinases; phosphorylation; cancers; inflammatory diseases; protein kinase inhibitors; anticancer drugs
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Special Issue Information

Dear Colleagues,

Protein kinases are enzymes that transfer ATP-γ-phosphate to the hydroxy groups of serine, threonine, and tyrosine residues of substrate proteins. Through phosphorylation of substrate proteins, protein kinases regulate their biological activity, cellular location, and interaction with other proteins to conduct signal transduction for cell proliferation, differentiation, and metabolism. The fine tuning of protein phosphorylation is crucial for orchestrating protein networks, which are essential for vital functions.  A total of 518 putative protein kinases have been identified in the human genome. They are divided into serine/threonine kinases and tyrosine kinases. The former group is further divided into seven subgroups (AGC, CAMK, CK1, CMGC, RGC, STE, and TKL), while the latter group is divided into two subgroups (receptor type and non-receptor type). Abnormality of protein kinases due to chromosomal mutation, translocation and deletion, aberrant splicing, and protein overexpression and loss of function is involved in developmental anomalies and various diseases such as cancers, inflammatory diseases, and metabolic disorders (e.g., diabetes mellitus). It is also related to the occurrence of cardiovascular diseases, neuronal degeneration, immune dysregulation, renal diseases, and sense organ disorders. Therapeutic strategies targeting these protein kinases are being explored. This has already led to the discovery of more than 40 protein kinase inhibitors as anticancer drugs. Further analysis of protein kinases associated with diseases and the development of novel protein kinase inhibitors may help to overcome intractable diseases.

Dr. Manae Suzuki Kurokawa
Guest Editor

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Keywords

  • protein kinases
  • phosphorylation
  • cancers
  • inflammatory diseases
  • protein kinase inhibitors
  • anticancer drugs

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Published Papers (1 paper)

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Research

12 pages, 4644 KiB  
Article
Molecular Dynamics Simulations of the SPRED2Leu100Pro EVH-1 Domain Complexed with the GAP-Related Domain of Neurofibromin
by Martina Terrusa, Elisa Sangiovanni, Marialetizia Motta, Marco Tartaglia, Ingrid Guarnetti Prandi and Giovanni Chillemi
Int. J. Mol. Sci. 2025, 26(9), 4342; https://doi.org/10.3390/ijms26094342 - 2 May 2025
Viewed by 321
Abstract
The homozygous Leu100Pro amino acid substitution in SPRED2, a protein negatively controlling RAS function, has recently been identified to be causally linked to a recessive form of Noonan syndrome. The amino acid substitution was documented to affect protein stability and cause a decreased [...] Read more.
The homozygous Leu100Pro amino acid substitution in SPRED2, a protein negatively controlling RAS function, has recently been identified to be causally linked to a recessive form of Noonan syndrome. The amino acid substitution was documented to affect protein stability and cause a decreased and/or less stable interaction with neurofibromin, a RAS-specific GTPase activating protein negatively regulating RAS function. To further investigate the structural and functional impact of Leu100Pro, we structurally characterized the consequences of this change on the interaction of SPRED2 with neurofibromin, by 1 µn-long molecular dynamics (MD) simulations. Our analyses failed in identifying local perturbations predicted to disrupt or dramatically affect SPRED2 binding to neurofibromin, though a rearrangement of their interaction was observed. On the other hand, MD simulations also identified long-range structural rearrangements of the SPRED2 EVH-1 domain, which might be relevant for an aberrant folding of the mutant driving the previously documented accelerated degradation. Overall, the performed MD simulations suggest the occurrence of multiple intramolecular and intermolecular structural perturbations driven by the Leu100Pro change that likely contribute to its LoF behavior. Full article
(This article belongs to the Special Issue Protein Kinase in Disease, 2nd Edition)
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