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The Role of Protein Kinase in Health and Diseases
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The Role of Protein Kinase in Health and Diseases

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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 3912

Special Issue Editor

Dr. Manuela Loi

E-Mail Website
Guest Editor
Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126 Bologna, Italy
Interests: protein kinases; phosphorylation; CDKL5; neurological disorder; targeted therapies

Special Issue Information

Dear Colleagues,

Protein kinases are enzymes that modify other proteins by adding phosphate groups, playing a vital role in cellular processes such as growth, differentiation, and apoptosis. They are classified into two main types: serine/threonine kinases, which target serine and threonine residues, and tyrosine kinases, which phosphorylate tyrosine residues. Dysregulated kinase activity is linked to various diseases, including cancer, neurological disorders (such as Alzheimer's and Parkinson's), and metabolic diseases like diabetes and obesity. Abnormal kinase function can lead to uncontrolled cell proliferation and disrupt essential signaling pathways. Understanding the roles of protein kinases in disease is crucial for developing targeted therapies aimed at restoring cellular balance and improving patient outcomes. This Special Issue calls for original research and reviews on protein kinases in disease and potential therapeutic interventions.

Dr. Manuela Loi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • protein kinases
  • phosphorylation
  • cancer
  • neurological disorder
  • targeted therapies
  • metabolic diseases

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Published Papers (4 papers)

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Research

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31 pages, 5062 KB  
Article
Functional Analysis of the PI3K/AKT/mTOR Pathway Inhibitor, Gedatolisib, Plus Fulvestrant with and Without Palbociclib in Breast Cancer Models
by Aaron Broege, Stefano Rossetti, Adrish Sen, Ann De La Forest, Laura Davis, Megan Seibel, Arul S. Menon, Sydney Stokke, Allison Macaulay, Jhomary Molden and Lance Laing
Int. J. Mol. Sci. 2025, 26(12), 5844; https://doi.org/10.3390/ijms26125844 - 18 Jun 2025
Viewed by 1091
Abstract
Treatment with endocrine therapy (ET) in combination with CDK4/6 inhibitors has improved the outcome of patients with hormone receptor (HR)+/HER2- advanced breast cancer (ABC), but most patients eventually experience disease progression. Since the PI3K-AKT-mTOR (PAM), estrogen receptor (ER), and cyclin-dependent kinase (CDK) pathways [...] Read more.
Treatment with endocrine therapy (ET) in combination with CDK4/6 inhibitors has improved the outcome of patients with hormone receptor (HR)+/HER2- advanced breast cancer (ABC), but most patients eventually experience disease progression. Since the PI3K-AKT-mTOR (PAM), estrogen receptor (ER), and cyclin-dependent kinase (CDK) pathways are interdependent drivers of HR+/HER2- breast cancer (BC), the simultaneous inhibition of these pathways is expected to enhance anti-tumor control. Here we investigated the molecular and cellular effects of gedatolisib, a multi-target kinase inhibitor of the PAM pathway currently being evaluated in Phase 3 clinical trials, combined with fulvestrant and/or palbociclib in BC cell models. We found that the gedatolisib/fulvestrant/palbociclib triplet inhibited BC cell growth significantly more than the single agents or the palbociclib/fulvestrant doublet, both in vitro and vivo. Specifically, the triplet combination counteracted adaptive responses associated with single drug treatment, such as the reactivation of the CDK-RB-E2F pathway after palbociclib treatment, and inhibited multiple cellular functions, such as cell cycle progression, cell survival, protein synthesis, and glucose metabolism. The triplet combination was effective in treatment-naïve BC cell lines as well as in cell lines adapted to palbociclib and/or fulvestrant, regardless of PIK3CA/PTEN genetic alterations. Our findings provide a mechanistic rationale for conducting clinical studies evaluating gedatolisib in combination with CDK4/6 inhibitors and ET in HR+/HER2- ABC. Full article
(This article belongs to the Special Issue The Role of Protein Kinase in Health and Diseases)
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Review

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27 pages, 1739 KB  
Review
The Link Between Dietary Timing and Exercise Performance Through Adipocyte AMPKα2 Signaling
by Sohyun Kim, Jihyun Baek and Man S. Kim
Int. J. Mol. Sci. 2025, 26(13), 6061; https://doi.org/10.3390/ijms26136061 - 24 Jun 2025
Viewed by 738
Abstract
Emerging evidence suggests that the timing of eating and exercise over the course of the day is paramount to metabolism and physical function. This review highlights seminal studies showing that adipocyte AMPKα2 signaling controls circadian adipose tissue–skeletal muscle communication. Day-restricted feeding has been [...] Read more.
Emerging evidence suggests that the timing of eating and exercise over the course of the day is paramount to metabolism and physical function. This review highlights seminal studies showing that adipocyte AMPKα2 signaling controls circadian adipose tissue–skeletal muscle communication. Day-restricted feeding has been shown to improve exercise performance via adipocyte-specific activation of AMPKα2, which controls fat–muscle crosstalk in a time-of-day dependent manner. This review also discusses corroborating experimental studies designating mesenchymal stem cells as key cellular mediators, showing that exercise in the afternoon leads to better metabolic effects in humans, and illustrating how incorrect timing of food intake leads to leptin resistance and metabolic dysregulation. Multi-omics strategies have shed light on the molecular mechanisms underlying such effects of time, showing the circadian control of metabolic processes across tissues. These results advance our knowledge of chronometabolism and offer exciting temporal intervention treatments for metabolic diseases, such as time-restricted feeding, timed exercise, and chronopharmacological targeting of AMPK. Fat–muscle crosstalk, physical performance, and metabolic health outcomes can possibly be optimized by synchronizing dietary and exercise timing with endogenous circadian rhythms. Full article
(This article belongs to the Special Issue The Role of Protein Kinase in Health and Diseases)
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21 pages, 1279 KB  
Review
Metformin in Colorectal Cancer: Epidemiological Evidence, Predictive Biomarkers, and Implications for Prevention and Treatment
by Seokho Myung, Youn Young Park and Man S. Kim
Int. J. Mol. Sci. 2025, 26(13), 6040; https://doi.org/10.3390/ijms26136040 - 24 Jun 2025
Viewed by 1068
Abstract
Interest in metformin as a potential anticancer agent for colorectal cancer (CRC) has increased. However, compelling epidemiological links and strong preclinical evidence suggest that metformin has variable efficacy in patients with CRC. This variability highlights the need to identify the patients who are [...] Read more.
Interest in metformin as a potential anticancer agent for colorectal cancer (CRC) has increased. However, compelling epidemiological links and strong preclinical evidence suggest that metformin has variable efficacy in patients with CRC. This variability highlights the need to identify the patients who are most likely to benefit from effective stratification. We aimed to review the evidence concerning the diverse roles of metformin in CRC prevention and treatment, focusing on identifying and validating the predictive biomarkers essential for selecting patient subgroups that are likely to respond positively. We explored the various molecular pathways through which metformin acts and investigated how these diverse mechanisms might explain the observed differences in patient responses. Epidemiological studies and large meta-analyses have consistently reported reduced CRC incidence and improved survival among patients with diabetes treated with metformin. However, successfully extending these benefits broadly across all patients with CRC or achieving predictable outcomes in advanced disease settings remains a significant challenge. This review consolidates the current knowledge, highlights how different mechanisms interact, critically assesses clinical evidence in light of patient heterogeneity, and advocates for the development and implementation of biomarker-guided personalized therapeutic strategies as key to optimally utilizing the potential of metformin in CRC management. The current challenges and vital future research priorities in this critical area are also outlined. Full article
(This article belongs to the Special Issue The Role of Protein Kinase in Health and Diseases)
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17 pages, 2031 KB  
Review
Protein Kinase CK2 Inhibition Represents a Pharmacological Chance for the Treatment of Skin Diseases
by Michele Scuruchi, Desirèe Speranza, Giuseppe Bruschetta, Federico Vaccaro, Mariarosaria Galeano, Giovanni Pallio, Mario Vaccaro, Francesco Borgia, Federica Li Pomi, Massimo Collino and Natasha Irrera
Int. J. Mol. Sci. 2025, 26(11), 5404; https://doi.org/10.3390/ijms26115404 - 4 Jun 2025
Viewed by 748
Abstract
Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and [...] Read more.
Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and inflammatory dermatoses. CK2 overactivation fosters keratinocyte proliferation and pro-inflammatory cytokine production through the STAT3 and Akt pathways in psoriasis, thus contributing to epidermal hyperplasia and inflammation. In the realm of oncology, CK2 overexpression correlates with tumor progression, facilitating cell survival and metastasis in melanoma and non-melanoma skin cancers. Pharmacological inhibition of CK2 has demonstrated therapeutic potential, with CX-4945 (Silmitasertib) as the most studied adenosine triphosphate-competitive inhibitor (ATP-competitive inhibitor). Preclinical models reveal that CK2 inhibitors effectively mitigate pathological features of psoriasis, regulate keratinocyte differentiation, and suppress tumor growth in skin cancers. These inhibitors also potentiate the efficacy of conventional chemotherapeutics and exhibit anti-inflammatory effects in dermatological conditions. Future research will aim to enhance the specificity and delivery of CK2-targeting therapies, including topical formulations, to minimize systemic side effects. Combination therapies integrating CK2 inhibitors with other agents might offer synergistic benefits in managing skin diseases. This review underscores CK2’s critical role in skin and its therapeutic potential as a pharmacological target, advocating for innovative approaches to harness CK2 inhibition in dermatology. Full article
(This article belongs to the Special Issue The Role of Protein Kinase in Health and Diseases)
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