Targeting GRK5 for Treating Chronic Degenerative Diseases
G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, call...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1920 |
| _version_ | 1797396508781314048 |
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| author | Federica Marzano Antonio Rapacciuolo Nicola Ferrara Giuseppe Rengo Walter J. Koch Alessandro Cannavo |
| author_facet | Federica Marzano Antonio Rapacciuolo Nicola Ferrara Giuseppe Rengo Walter J. Koch Alessandro Cannavo |
| author_sort | Federica Marzano |
| collection | DOAJ |
| description | G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote “non-canonical” signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases. |
| first_indexed | 2024-03-09T00:51:19Z |
| format | Article |
| id | doaj.art-38448f3d33074fcaa18dacb967428ee2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:51:19Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-38448f3d33074fcaa18dacb967428ee22023-12-11T17:08:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224192010.3390/ijms22041920Targeting GRK5 for Treating Chronic Degenerative DiseasesFederica Marzano0Antonio Rapacciuolo1Nicola Ferrara2Giuseppe Rengo3Walter J. Koch4Alessandro Cannavo5Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, ItalyDepartment of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, ItalyCenter for Translational Medicine, Temple University, Philadelphia, PA 19140, USADepartment of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, ItalyG protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote “non-canonical” signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases.https://www.mdpi.com/1422-0067/22/4/1920cardiovascularneurodegenerationcancerGPCRGRK5 |
| spellingShingle | Federica Marzano Antonio Rapacciuolo Nicola Ferrara Giuseppe Rengo Walter J. Koch Alessandro Cannavo Targeting GRK5 for Treating Chronic Degenerative Diseases International Journal of Molecular Sciences cardiovascular neurodegeneration cancer GPCR GRK5 |
| title | Targeting GRK5 for Treating Chronic Degenerative Diseases |
| title_full | Targeting GRK5 for Treating Chronic Degenerative Diseases |
| title_fullStr | Targeting GRK5 for Treating Chronic Degenerative Diseases |
| title_full_unstemmed | Targeting GRK5 for Treating Chronic Degenerative Diseases |
| title_short | Targeting GRK5 for Treating Chronic Degenerative Diseases |
| title_sort | targeting grk5 for treating chronic degenerative diseases |
| topic | cardiovascular neurodegeneration cancer GPCR GRK5 |
| url | https://www.mdpi.com/1422-0067/22/4/1920 |
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