Targeting GRK5 for Treating Chronic Degenerative Diseases

Federica Marzano, Antonio Rapacciuolo, Nicola Ferrara, Giuseppe Rengo, Walter J Koch, Alessandro Cannavo

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)1920
Number of pages17
JournalInt J Mol Sci
Issue number4
Publication statusPublished - Feb 15 2021


  • Animals
  • Cardiovascular Diseases/drug therapy
  • G-Protein-Coupled Receptor Kinase 5/antagonists & inhibitors
  • Humans
  • Molecular Targeted Therapy/methods
  • Neoplasms/drug therapy
  • Neurodegenerative Diseases/drug therapy
  • Receptors, G-Protein-Coupled/metabolism
  • Signal Transduction


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