scholarly journals Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
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. [225, 529, 578, 583, 584, 742, 753, 444, 10].

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 Regulators of G protein Signaling (RGS) proteins (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (5) ◽  
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. [183, 411, 446, 450, 451, 558, 566, 345, 9].

scholarly journals Regulators of G protein Signaling (RGS) proteins (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Mohammed Alqinyah ◽  
Christopher Bodle ◽  
Josephine Bou Dagher ◽  
Bandana Chakravarti ◽  
Shreoshi P. Choudhuri ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
G Protein ◽  
G Proteins ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Gtp Hydrolysis ◽  
G Protein Signalling ◽  
Rgs Domain

Regulators of G protein signalling (RGS) proteins display a common RGS domain that interacts with the GTP-bound Gα subunits of heterotrimeric G proteins, enhancing GTP hydrolysis by stabilising the transition state [29, 419, 418], leading to a termination of GPCR signalling. Interactions through protein:protein interactions of many RGS proteins have been identified for targets other than heteromeric G proteins. Sequence analysis of the 20 RGS proteins suggests four families of RGS: RZ, R4, R7 and R12 families. Many of these proteins have been identified to have effects other than through targetting G proteins. Included here is RGS4 for which a number of pharmacological inhibitors have been described.

scholarly journals G protein signaling governing cell fate decisions involves opposing Gα subunits inCryptococcus neoformans

2007 ◽  
Vol 18 (9) ◽  
pp. 3237-3249 ◽  
Author(s):  
Yen-Ping Hsueh ◽  
Chaoyang Xue ◽  
Joseph Heitman
Keyword(s):  
G Protein ◽  
Cell Fate ◽  
G Protein Coupled Receptors ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Pheromone Receptor ◽  
Cell Fate Decisions ◽  
Regulatory Circuit ◽  
Receptor Recognition ◽  
G Protein Coupled

Communication between cells and their environments is often mediated by G protein-coupled receptors and cognate G proteins. In fungi, one such signaling cascade is the mating pathway triggered by pheromone/pheromone receptor recognition. Unlike Saccharomyces cerevisiae, which expresses two Gα subunits, most filamentous ascomycetes and basidiomycetes have three Gα subunits. Previous studies have defined the Gα subunit acting upstream of the cAMP-protein kinase A pathway, but it has been unclear which Gα subunit is coupled to the pheromone receptor and response pathway. Here we report that in the pathogenic basidiomycetous yeast Cryptococcus neoformans, two Gα subunits (Gpa2, Gpa3) sense pheromone and govern mating. gpa2 gpa3 double mutants, but neither gpa2 nor gpa3 single mutants, are sterile in bilateral crosses. By contrast, deletion of GPA3 (but not GPA2) constitutively activates pheromone response and filamentation. Expression of GPA2 and GPA3 is differentially regulated: GPA3 expression is induced by nutrient-limitation, whereas GPA2 is induced during mating. Based on the phenotype of dominant active alleles, Gpa2 and Gpa3 signal in opposition: Gpa2 promotes mating, whereas Gpa3 inhibits. The incorporation of an additional Gα into the regulatory circuit enabled increased signaling complexity and facilitated cell fate decisions involving choice between yeast growth and filamentous asexual/sexual development.

scholarly journals Contribution of AT1R mechanoactivation to the arterial myogenic response and its regulation by RGS5 protein in skeletal muscle arterioles

2015 ◽  
Author(s):  
◽  
Kwangseok Hong
Keyword(s):  
G Protein ◽  
Mechanical Stimulus ◽  
G Protein Coupled Receptors ◽  
G Protein Signaling ◽  
Myogenic Response ◽  
Protein Signaling ◽  
Regulatory Molecule ◽  
Cytoskeleton Reorganization ◽  
G Protein Coupled

Although intracellular mechanisms underlying the arteriolar myogenic response have been well-defined, the mechanotransduction events transducing the mechanical stimulus remain unclear. Recently, ligand-independent activation of G protein-coupled receptors (in particular, the angiotensin II type 1 receptor; AT1R) has been suggested to play a major role in vascular smooth muscle mechanotransduction, thereby contributing to myogenic constriction. However, the downstream pathways following ligand-independent activation of the AT1R have not been clearly elucidated. Our studies provide pharmacological evidence that the mechanically activated AT1R generates diacylglycerol which in turn activates PKC that subsequently induces actin cytoskeleton reorganization for myogenic constriction. In terms of physiological roles, the arterial myogenic response acts to generate vascular tone, prevent capillaries from being damaged, and reduce edema due to high capillary hydrostatic pressure. Thus, an exaggerated AT1R-mediated myogenic constriction could conceivably contribute to vascular disorders. As a result, small arteries likely exhibit negative feedback regulatory mechanisms to prevent such an exaggerated myogenic response. In regard to this, we discovered that ligand-dependent or-independent activation of the AT1R causes trafficking of an important regulatory molecule, RGS5 (Regulators of G protein Signaling) protein, which may modulate Ang II or myogenic-mediated constriction by terminating Gq/11 protein-dependent signaling.

scholarly journals Localization of Giα proteins in the centrosomes and at the midbody: implication for their role in cell division

2007 ◽  
Vol 178 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Hyeseon Cho ◽  
John H. Kehrl
Keyword(s):  
Cell Division ◽  
G Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Direct Interaction ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Independent Functions ◽  
G Protein Coupled

At the plasma membrane, heterotrimeric G proteins act as molecular switches to relay signals from G protein–coupled receptors; however, Gα subunits also have receptor-independent functions at intracellular sites. Regulator of G protein signaling (RGS) 14, which enhances the intrinsic GTPase activity of Giα proteins, localizes in centrosomes, which suggests the coexpression of Giα. We show expression of Giα1, Giα2, and Giα3 in the centrosomes and at the midbody. Fluorescence resonance energy transfer analysis confirms a direct interaction between RGS14 and Giα1 in centrosomes. Expression of GTPase-deficient Giα1 results in defective cytokinesis, whereas that of wild-type or GTPase-deficient Giα3 causes prolonged mitosis. Cells treated with pertussis toxin, with reduced expression of Giα1, Giα2, and Giα3 or with decreased expression of RGS14 also exhibit cytokinesis defects. These results suggest that Giα proteins and their regulators at these sites may play essential roles during mammalian cell division.

scholarly journals GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes

2012 ◽  
Vol 197 (6) ◽  
pp. 711-719 ◽  
Author(s):  
Cesare Orlandi ◽  
Ekaterina Posokhova ◽  
Ikuo Masuho ◽  
Thomas A. Ray ◽  
Nazarul Hasan ◽  
...  
Keyword(s):  
G Protein ◽  
Night Vision ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Gpcr Signaling ◽  
Signaling Specificity ◽  
Orphan Gpcrs ◽  
G Protein Coupled

The extent and temporal characteristics of G protein–coupled receptor (GPCR) signaling are shaped by the regulator of G protein signaling (RGS) proteins, which promote G protein deactivation. With hundreds of GPCRs and dozens of RGS proteins, compartmentalization plays a key role in establishing signaling specificity. However, the molecular details and mechanisms of this process are poorly understood. In this paper, we report that the R7 group of RGS regulators is controlled by interaction with two previously uncharacterized orphan GPCRs: GPR158 and GPR179. We show that GPR158/179 recruited RGS complexes to the plasma membrane and augmented their ability to regulate GPCR signaling. The loss of GPR179 in a mouse model of night blindness prevented targeting of RGS to the postsynaptic compartment of bipolar neurons in the retina, illuminating the role of GPR179 in night vision. We propose that the interaction of RGS proteins with orphan GPCRs promotes signaling selectivity in G protein pathways.

scholarly journals Stachel-independent modulation of GPR56/ADGRG1 signaling by synthetic ligands directed to its extracellular region

2017 ◽  
Vol 114 (38) ◽  
pp. 10095-10100 ◽  
Author(s):  
Gabriel S. Salzman ◽  
Shu Zhang ◽  
Ankit Gupta ◽  
Akiko Koide ◽  
Shohei Koide ◽  
...  
Keyword(s):  
G Protein ◽  
Cancer Progression ◽  
G Protein Coupled Receptors ◽  
G Protein Signaling ◽  
Biological Processes ◽  
Protein Signaling ◽  
Extracellular Region ◽  
Mechanistic Analysis ◽  
Signaling Domains ◽  
G Protein Coupled

Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse biological processes, including neurodevelopment and cancer progression. aGPCRs are characterized by large and diverse extracellular regions (ECRs) that are autoproteolytically cleaved from their membrane-embedded signaling domains. Although ECRs regulate receptor function, it is not clear whether ECRs play a direct regulatory role in G-protein signaling or simply serve as a protective cap for the activating “Stachel” sequence. Here, we present a mechanistic analysis of ECR-mediated regulation of GPR56/ADGRG1, an aGPCR with two domains [pentraxin and laminin/neurexin/sex hormonebinding globulin-like (PLL) and G protein-coupled receptor autoproteolysis-inducing (GAIN)] in its ECR. We generated a panel of high-affinity monobodies directed to each of these domains, from which we identified activators and inhibitors of GPR56-mediated signaling. Surprisingly, these synthetic ligands modulated signaling of a GPR56 mutant defective in autoproteolysis and hence, inStachelpeptide exposure. These results provide compelling support for a ligand-induced and ECR-mediated mechanism that regulates aGPCR signaling in a transient and reversible manner, which occurs in addition to theStachel-mediated activation.

scholarly journals How a Mycoparasite Employs G-Protein Signaling: Using the Example of Trichoderma

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Markus Omann ◽  
Susanne Zeilinger
Keyword(s):  
G Protein ◽  
Pathogenic Fungi ◽  
G Protein Coupled Receptors ◽  
Host Recognition ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Lytic Enzymes ◽  
Antifungal Metabolites ◽  
Downstream Effectors ◽  
G Protein Coupled

Mycoparasitic Trichoderma spp. act as potent biocontrol agents against a number of plant pathogenic fungi, whereupon the mycoparasitic attack includes host recognition followed by infection structure formation and secretion of lytic enzymes and antifungal metabolites leading to the host's death. Host-derived signals are suggested to be recognized by receptors located on the mycoparasite's cell surface eliciting an internal signal transduction cascade which results in the transcription of mycoparasitism-relevant genes. Heterotrimeric G proteins of fungi transmit signals originating from G-protein-coupled receptors mainly to the cAMP and the MAP kinase pathways resulting in regulation of downstream effectors. Components of the G-protein signaling machinery such as G subunits and G-protein-coupled receptors were recently shown to play crucial roles in Trichoderma mycoparasitism as they govern processes such as the production of extracellular cell wall lytic enzymes, the secretion of antifungal metabolites, and the formation of infection structures.

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