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Review
. 2025 Mar 5:2025:8837640.
doi: 10.1155/mi/8837640. eCollection 2025.

Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics

Xizhuang Gao  1 , Dehuai Jing  1 , Yaowen Zhang  1 , Fengqin Zhu  1 , Yonghong Yang  2 , Guangxi Zhou  1
Affiliations
Review

Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics

Xizhuang Gao et al. Mediators Inflamm. .

Abstract

G protein-coupled receptors (GPCRs) represent humans' most prominent family of membrane proteins. In contrast, G protein-coupled receptor kinases (GRKs) play a pivotal role in the rapid desensitization of GPCRs. GRK2 is a particularly significant member of the GRK family. Recent studies have demonstrated that GRK2 primarily regulates immune cell function and homeostasis through receptor desensitization. Over the past decade, substantial progress has been made in elucidating the role of GRK2 in various human diseases. Notably, GRK2 is implicated in a range of autoimmune disorders, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), Sjögren's syndrome (SS), autoimmune myocarditis, hepatitis, and Graves' disease. Furthermore, emerging research has expanded our understanding of GRK2's involvement in cancer biology. Comprehensive investigations into the biological and pathological functions of GRK2 have facilitated the development of therapeutic strategies aimed at targeting the GRK2 signaling pathway in cancer, inflammation, and autoimmune diseases. Promising results have been observed with targeted biologics in preclinical and clinical trials. This review aims to elucidate the multifaceted role of GRK2 in immune function, autoimmune diseases, and cancer to uncover the remaining complexities associated with this kinase. A thorough understanding of GRK2 may position it as a potent therapeutic target in treating inflammation and cancer.

Keywords: GRK2; autoimmune diseases; cancer; immune cell; therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Structural organization and functional role of GRK2.
Figure 2
Figure 2
GRK2 is a key regulator of immune cell function, influencing various aspects of immune responses and cancer progression. This figure illustrates the role of GRK2 across different immune cell types, including T cells, B cells, neutrophils, macrophages, and mast cells. GRK2 modulates T cell receptor signaling, B cell motility, neutrophil migration, macrophage polarization, and mast cell degranulation, highlighting its pivotal role in maintaining immune balance. Dysregulation of GRK2 levels is implicated in autoimmune diseases and cancer, suggesting its potential as a therapeutic target for restoring immune system function.
Figure 3
Figure 3
Influence of GRK2 on immune diseases and cancer.
See this image and copyright information in PMC

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References

    1. Langan D., Kim E. Y., Moudgil K. D. Modulation of Autoimmune Arthritis by Environmental “Hygiene” and Commensal Microbiota. Cellular Immunology . 2019;339:59–67. doi: 10.1016/j.cellimm.2018.12.005. - DOI - PMC - PubMed
    1. Song L., Wang Y., Zhang J., Song N., Xu X., Lu Y. The Risks of Cancer Development in Systemic Lupus Erythematosus (SLE) Patients: A Systematic Review and Meta-Analysis. Arthritis Research & Therapy . 2018;20(1) doi: 10.1186/s13075-018-1760-3. - DOI - PMC - PubMed
    1. Carretta M. D., Quiroga J., López R., Hidalgo M. A., Burgos R. A. Participation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer. Frontiers in Physiology . 2021;12 doi: 10.3389/fphys.2021.662739.662739 - DOI - PMC - PubMed
    1. Edwardson D. W., Parissenti A. M., Kovala A. T. Chemotherapy and Inflammatory Cytokine Signalling in Cancer Cells and the Tumour Microenvironment. Advances in Experimental Medicine and Biology . 2019;1152:173–215. doi: 10.1007/978-3-030-20301-6. - DOI - PubMed
    1. Hauser A. S., Attwood M. M., Rask-Andersen M., Schiöth H. B., Gloriam D. E. Trends in GPCR Drug Discovery: New Agents, Targets and Indications. Nature Reviews Drug Discovery . 2017;16(12):829–842. doi: 10.1038/nrd.2017.178. - DOI - PMC - PubMed

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