Journal article
Introduction: G Protein-coupled Receptors and RGS Proteins
Progress in molecular biology and translational science, Vol.133, pp.1-11
2015
DOI: 10.1016/bs.pmbts.2015.03.002
PMID: 26123299
Abstract
Here, we provide an overview of the role of regulator of G protein-signaling (RGS) proteins in signaling by G protein-coupled receptors (GPCRs), the latter of which represent the largest class of cell surface receptors in humans responsible for transducing diverse extracellular signals into the intracellular environment. Given that GPCRs regulate virtually every known physiological process, it is unsurprising that their dysregulation plays a causative role in many human diseases and they are targets of 40-50% of currently marketed pharmaceuticals. Activated GPCRs function as GTPase exchange factors for Gα subunits of heterotrimeric G proteins, promoting the formation of Gα-GTP and dissociated Gβγ subunits that regulate diverse effectors including enzymes, ion channels, and protein kinases. Termination of signaling is mediated by the intrinsic GTPase activity of Gα subunits leading to reformation of the inactive Gαβγ heterotrimer. RGS proteins determine the magnitude and duration of cellular responses initiated by many GPCRs by functioning as GTPase-accelerating proteins (GAPs) for specific Gα subunits. Twenty canonical mammalian RGS proteins, divided into four subfamilies, act as functional GAPs while almost 20 additional proteins contain nonfunctional RGS homology domains that often mediate interaction with GPCRs or Gα subunits. RGS protein biochemistry has been well elucidated in vitro, but the physiological functions of each RGS family member remain largely unexplored. This book summarizes recent advances employing modified model organisms that reveal RGS protein functions in vivo, providing evidence that RGS protein modulation of G protein signaling and GPCRs can be as important as initiation of signaling by GPCRs.
Details
- Title: Subtitle
- Introduction: G Protein-coupled Receptors and RGS Proteins
- Creators
- Adele Stewart - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USARory A Fisher - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. Electronic address: rory-fisher@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Progress in molecular biology and translational science, Vol.133, pp.1-11
- Publisher
- Netherlands
- DOI
- 10.1016/bs.pmbts.2015.03.002
- PMID
- 26123299
- ISSN
- 1877-1173
- eISSN
- 1878-0814
- Grant note
- R01 CA161882 / NCI NIH HHS T32 MH065215 / NIMH NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040393302771
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