GRK2 in cardiovascular disease and its potential as a therapeutic target

Ferrero, Kimberly; Koch, Walter J.

doi:10.1016/j.yjmcc.2022.07.008

Cited by 12 publications

(5 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…GRK2 plays a key role in regulating numerous physiological and pathophysiological processes [ 10 , 12 , 18 ]. For example, increased GRK2 levels and/or enhanced GRK2 activity are of critical importance for the development of heart failure [ 10 ]. For this reason, pharmacological inhibitors of cardiac GRK2 activity are predicted to prove useful as cardioprotective drugs [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, increased GRK2 levels and/or enhanced GRK2 activity are of critical importance for the development of heart failure [ 10 ]. For this reason, pharmacological inhibitors of cardiac GRK2 activity are predicted to prove useful as cardioprotective drugs [ 10 ]. Additional studies have shown that changes in GRK2 activity can also affect systemic glucose homeostasis and insulin sensitivity of peripheral tissues, suggesting that GRK2 inhibitors could be beneficial for treating type 2 diabetes and related metabolic disorders [ 12 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…The receptor-associated arrestins also promote GPCR internalization via clathrin-coated pits [ [4] , [5] , [6] , [7] ]. While the metabolic functions of arrestins, in particular β-arrestin-1 and -2 (arrestin-2 and -3, respectively), have been studied in considerable detail [ 8 , 9 ], only a few studies have explored the metabolic relevance of GRKs under physiological and pathophysiological conditions, except for a vast body of research focusing on the important role of GRK2 in the cardiovascular system [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice

Oteng,

Pittala,

Kliewer

et al. 2024

Molecular Metabolism

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatic GRK2 is dispensable for glucose homeostasis and other key metabolic parameters in mice

Oteng,

Pittala,

Kliewer

et al. 2024

Molecular Metabolism

View full text Add to dashboard Cite

“…115 Receptor-activated β-arrestin also serves as a scaffold and allosteric activator for protein kinase signaling cascades, amplifying the activity of these pathways within cells. These include MAPK (mitogen-activated protein kinases), PI3K, AKT (protein kinase B), and sarcoma 57,103,[117][118][119][120] in addition to a wide range of other pathways. 121 G-protein and β-arrestin-mediated signaling display different spatial and temporal profiles, 122 although this can vary significantly among receptors.…”

Section: β-Arrestins: Canonical Gpcr Transducersmentioning

confidence: 99%

G Protein-Coupled Receptors: A Century of Research and Discovery

Liu,

Anderson,

Rajagopal

et al. 2024

Circulation Research

View full text Add to dashboard Cite

GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs regulate nearly every aspect of human physiology and disease, thus serving as important drug targets in cardiovascular disease. Sharing a conserved structure comprised of 7 transmembrane α-helices, GPCRs couple to heterotrimeric G-proteins, GPCR kinases, and β-arrestins, promoting downstream signaling through second messengers and other intracellular signaling pathways. GPCR drug development has led to important cardiovascular therapies, such as antagonists of β-adrenergic and angiotensin II receptors for heart failure and hypertension, and agonists of the glucagon-like peptide-1 receptor for reducing adverse cardiovascular events and other emerging indications. There continues to be a major interest in GPCR drug development in cardiovascular and cardiometabolic disease, driven by advances in GPCR mechanistic studies and structure-based drug design. This review recounts the rich history of GPCR research, including the current state of clinically used GPCR drugs, and highlights newly discovered aspects of GPCR biology and promising directions for future investigation. As additional mechanisms for regulating GPCR signaling are uncovered, new strategies for targeting these ubiquitous receptors hold tremendous promise for the field of cardiovascular medicine.

show abstract