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The role of serine/threonine protein kinases in cardiovascular disease and potential therapeutic methods - 23/07/24

Doi : 10.1016/j.biopha.2024.117093 
Yanjiao Wu a, Yuanming Zou a, Chunyu Song a, Kexin Cao a, Kexin Cai a, Shuxian Chen a, Zhaobo Zhang a, Danxi Geng a, Naijin Zhang a, b, c, , Hao Feng d, , Man Tang e, , Zhao Li a, , Guozhe Sun a, , Yixiao Zhang f, , Yingxian Sun a, b, g, , Ying Zhang a, b,
a Department of Cardiology, the First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province 110001, People’s Republic of China 
b Institute of health sciences, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, Liaoning Province 110001, People’s Republic of China 
c Key Laboratory of Reproductive and Genetic Medicine (China Medical University), National Health Commission, Shenyang 110004, China 
d Department of Ophthalmology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province 110001, People’s Republic of China 
e Department of clinical pharmacology, College of Pharmacy, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, Liaoning Province 110001, People’s Republic of China 
f Department of Urology Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, People’s Republic of China 
g Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, Liaoning Province 110001, People’s Republic of China 

Correspondence to: Department of Cardiology, the First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.Department of Cardiology, the First Hospital of China Medical UniversityShenyangLiaoningPeople's Republic of China⁎⁎Corresponding authors.

Abstract

Protein phosphorylation is an important link in a variety of signaling pathways, and most of the important life processes in cells involve protein phosphorylation. Based on the amino acid residues of phosphorylated proteins, protein kinases can be categorized into the following families: serine/threonine protein kinases, tyrosine-specific protein kinases, histidine-specific protein kinases, tryptophan kinases, and aspartate/glutamyl protein kinases. Of all the protein kinases, most are serine/threonine kinases, where serine/threonine protein kinases are protein kinases that catalyze the phosphorylation of serine or threonine residues on target proteins using ATP as a phosphate donor. The current socially accepted classification of serine/threonine kinases is to divide them into seven major groups: protein kinase A, G, C (AGC), CMGC, Calmodulin-dependent protein kinase (CAMK), Casein kinase (CK1), STE, Tyrosine kinase (TKL) and others. After decades of research, a preliminary understanding of the specific classification and respective functions of serine/threonine kinases has entered a new period of exploration. In this paper, we review the literature of the previous years and introduce the specific signaling pathways and related therapeutic modalities played by each of the small protein kinases in the serine/threonine protein kinase family, respectively, in some common cardiovascular system diseases such as heart failure, myocardial infarction, ischemia-reperfusion injury, and diabetic cardiomyopathy. To a certain extent, the current research results, including molecular mechanisms and therapeutic methods, are fully summarized and a systematic report is made for the prevention and treatment of cardiovascular diseases in the future.

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Graphical Abstract




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Highlights

Integrate the serine/threonine kinase system with the cardiovascular system and detail its molecular mechanism in the cardiovascular system.
Based on the description of the molecular mechanisms, animal and cellular experiments are utilized to support them.
This paper briefly lists the existing and potential drugs that are currently clinically targeting their molecular mechanisms.
Listed kinase families more closely associated with cardiovascular disease: AGC Protein Family; CMGC Protein Family; CAMK Protein Family.
By systematically describing the molecular mechanisms, cellular and animal experimental evidence, and clinically available drugs, it provides a theoretical basis for the future development of therapeutic drugs targeting serine/threonine kinases.

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Keywords : Cardiovascular disease, Serine/threonine protein kinases, Signaling pathway, Therapeutic methods


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Vol 177

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