title: Regulators of G-protein-signaling proteins: negative modulators of G-protein-coupled receptor signaling.
abstract: Regulators of G-protein-signaling (RGS) proteins are a category of intracellular proteins that have an inhibitory effect on the intracellular signaling produced by G-protein-coupled receptors (GPCRs). RGS along with RGS-like proteins switch on through direct contact G-alpha subunits providing a variety of intracellular functions through intracellular signaling. RGS proteins have a common RGS domain that binds to G alpha. RGS proteins accelerate GTPase and thus enhance guanosine triphosphate hydrolysis through the alpha subunit of heterotrimeric G proteins. As a result, they inactivate the G protein and quickly turn off GPCR signaling thus terminating the resulting downstream signals. Activity and subcellular localization of RGS proteins can be changed through covalent molecular changes to the enzyme, differential gene splicing, and processing of the protein. Other roles of RGS proteins have shown them to not be solely committed to being inhibitors but behave more as modulators and integrators of signaling. RGS proteins modulate the duration and kinetics of slow calcium oscillations and rapid phototransduction and ion signaling events. In other cases, RGS proteins integrate G proteins with signaling pathways linked to such diverse cellular responses as cell growth and differentiation, cell motility, and intracellular trafficking. Human and animal studies have revealed that RGS proteins play a vital role in physiology and can be ideal targets for diseases such as those related to addiction where receptor signaling seems continuously switched on.
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Woodard
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardín
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Berna-Erro
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain.
authors.forename: Gines M
authors.initials: GM
authors.lastname: Salido
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D021381:Protein Transport; D020710:RGS Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Cellular signaling pathways; G-protein-coupled receptors; G-protein-signaling proteins; GTPase; Signal transduction