title: Feedback regulation of G protein-coupled receptor signaling by GRKs and arrestins.
abstract: GPCRs are ubiquitous in mammalian cells and present intricate mechanisms for cellular signaling and communication. Mechanistically, GPCR signaling was identified to occur vectorially through heterotrimeric G proteins that are negatively regulated by GRK and arrestin effectors. Emerging evidence highlights additional roles for GRK and Arrestin partners, and establishes the existence of interconnected feedback pathways that collectively define GPCR signaling. GPCRs influence cellular dynamics and can mediate pathologic development, such as cancer and cardiovascular remolding. Hence, a better understanding of their overall signal regulation is of great translational interest and research continues to exploit the pharmacologic potential for modulating their activity.
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Black
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Premont
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, United States. Electronic address: ydaaka@ufl.edu.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Daaka
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D025461:Feedback, Physiological; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019390:Arrestins; D043562:Receptors, G-Protein-Coupled; D054768:G-Protein-Coupled Receptor Kinases
keywords: Arrestin; Biased signaling; G protein; GPCR; GRK; Signal transduction