scholarly journals Regulators of G protein signaling in cardiovascular function during pregnancy

2018 ◽  
Vol 50 (8) ◽  
pp. 590-604 ◽  
Author(s):  
Katherine J. Perschbacher ◽  
Guorui Deng ◽  
Rory A. Fisher ◽  
Katherine N. Gibson-Corley ◽  
Mark K. Santillan ◽  
...  
Keyword(s):  
G Protein ◽  
Gestational Hypertension ◽  
Expression Patterns ◽  
Second Messenger ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Specific Expression ◽  
Disease States ◽  
Signaling Mechanisms

G protein-coupled receptor signaling mechanisms are implicated in many aspects of cardiovascular control, and dysfunction of such signaling mechanisms is commonly associated with disease states. Investigators have identified a large number of regulator of G protein signaling (RGS) proteins that variously contribute to the modulation of intracellular second-messenger signaling kinetics. These many RGS proteins each interact with a specific set of second-messenger cascades and receptor types and exhibit tissue-specific expression patterns. Increasing evidence supports the contribution of RGS proteins, or their loss, in the pathogenesis of cardiovascular dysfunctions. This review summarizes the current understanding of the functional contributions of RGS proteins, particularly within the B/R4 family, in cardiovascular disorders of pregnancy including gestational hypertension, uterine artery dysfunction, and preeclampsia.

scholarly journals Regulators of G-Protein Signaling (RGS) Proteins: Region-Specific Expression of Nine Subtypes in Rat Brain

1997 ◽  
Vol 17 (20) ◽  
pp. 8024-8037 ◽  
Author(s):  
Stephen J. Gold ◽  
Yan G. Ni ◽  
Henrik G. Dohlman ◽  
Eric J. Nestler
Keyword(s):  
Rat Brain ◽  
G Protein ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Specific Expression

scholarly journals Regulators of G protein Signaling (RGS) proteins (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Katelin E. Ahlers-Dannen ◽  
Mohammed Alqinyah ◽  
Christopher Bodle ◽  
Josephine Bou Dagher ◽  
Bandana Chakravarti ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Signaling Cascades ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Gtp Hydrolysis ◽  
Rgs Domain ◽  
G Protein Coupled

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [160, 377, 411, 415, 416, 512, 519, 312, 6].

scholarly journals Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle

2012 ◽  
Vol 287 (21) ◽  
pp. 17870-17881 ◽  
Author(s):  
Swarup Roy Choudhury ◽  
Corey S. Westfall ◽  
John P. Laborde ◽  
Naveen C. Bisht ◽  
Joseph M. Jez ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Heterotrimeric G Protein

scholarly journals Probing the mutational landscape of regulators of G protein signaling proteins in cancer

2020 ◽  
Vol 13 (617) ◽  
pp. eaax8620 ◽  
Author(s):  
Vincent DiGiacomo ◽  
Marcin Maziarz ◽  
Alex Luebbers ◽  
Jillian M. Norris ◽  
Pandu Laksono ◽  
...  
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Mammalian Cells ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Loss Of Function ◽  
Gpcr Signaling ◽  
Mutational Landscape ◽  
Binding Interface

The advent of deep-sequencing techniques has revealed that mutations in G protein–coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulators of G protein signaling (RGS) proteins are critical modulators of GPCR signaling that dampen the activity of heterotrimeric G proteins through their GTPase-accelerating protein (GAP) activity, which is conferred by a conserved domain dubbed the “RGS-box.” Here, we developed an experimental pipeline to systematically assess the mutational landscape of RGS GAPs in cancer. A pan-cancer bioinformatics analysis of the 20 RGS domains with GAP activity revealed hundreds of low-frequency mutations spread throughout the conserved RGS domain structure with a slight enrichment at positions that interface with G proteins. We empirically tested multiple mutations representing all RGS GAP subfamilies and sampling both G protein interface and noninterface positions with a scalable, yeast-based assay. Last, a subset of mutants was validated using G protein activity biosensors in mammalian cells. Our findings reveal that a sizable fraction of RGS protein mutations leads to a loss of function through various mechanisms, including disruption of the G protein–binding interface, loss of protein stability, or allosteric effects on G protein coupling. Moreover, our results also validate a scalable pipeline for the rapid characterization of cancer-associated mutations in RGS proteins.

scholarly journals R4 RGS proteins: Regulation of G-protein signaling and beyond

2007 ◽  
Vol 116 (3) ◽  
pp. 473-495 ◽  
Author(s):  
Geetanjali Bansal ◽  
Kirk M. Druey ◽  
Zhihui Xie
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling
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