The Roles of GRKs in Hemostasis and Thrombosis
Open Access
- 28 July 2020
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (15), 5345
- https://doi.org/10.3390/ijms21155345
Abstract
Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.Funding Information
- Foundation for the National Institutes of Health (R01HL144574)
This publication has 112 references indexed in Scilit:
- G protein-coupled receptor kinases: More than just kinases and not only for GPCRsPharmacology & Therapeutics, 2012
- Arrestin-2 Differentially Regulates PAR4 and ADP Receptor Signaling in PlateletsOnline Journal of Public Health Informatics, 2011
- Polymorphisms in genes coding for GRK2 and GRK5 and response differences in antihypertensive-treated patientsPharmacogenetics and Genomics, 2011
- Cytoskeletal mechanics of proplatelet maturation and platelet releaseThe Journal of cell biology, 2010
- Platelet FormationSeminars in Hematology, 2010
- Identifying Patients at High Risk of a Cardiovascular Event in the Near FutureCirculation, 2010
- Agonist-selective, Receptor-specific Interaction of Human P2Y Receptors with β-Arrestin-1 and -2Online Journal of Public Health Informatics, 2008
- A GRK5 polymorphism that inhibits β-adrenergic receptor signaling is protective in heart failureNature Medicine, 2008
- Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosisProceedings of the National Academy of Sciences of the United States of America, 2007
- Clathrin Adaptor AP2 Regulates Thrombin Receptor Constitutive Internalization and Endothelial Cell ResensitizationMolecular and Cellular Biology, 2006