scholarly journals The G protein database, GproteinDb

2021 ◽  
Author(s):  
Gáspár Pándy-Szekeres ◽  
Mauricio Esguerra ◽  
Alexander S Hauser ◽  
Jimmy Caroli ◽  
Christian Munk ◽  
...  
Keyword(s):  
Human Physiology ◽  
G Protein ◽  
G Proteins ◽  
Reference Data ◽  
Genomic Data ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Protein Database ◽  
Sensory Stimuli ◽  
Protein Research

Abstract Two-thirds of signaling substances, several sensory stimuli and over one-third of drugs act via receptors coupling to G proteins. Here, we present an online platform for G protein research with reference data and tools for analysis, visualization and design of scientific studies across disciplines and areas. This platform may help translate new pharmacological, structural and genomic data into insights on G protein signaling vital for human physiology and medicine. The G protein database is accessible at https://gproteindb.org.

scholarly journals Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

2018 ◽  
Vol 70 (3) ◽  
pp. 446-474 ◽  
Author(s):  
Katherine E. Squires ◽  
Carolina Montañez-Miranda ◽  
Rushika R. Pandya ◽  
Matthew P. Torres ◽  
John R. Hepler
Keyword(s):  
Human Physiology ◽  
Genetic Analysis ◽  
G Protein ◽  
G Protein Signaling ◽  
Signaling Proteins ◽  
Protein Signaling

Multiple mechanisms of receptor-G protein signaling specificity

1995 ◽  
Vol 269 (2) ◽  
pp. F141-F158 ◽  
Author(s):  
J. R. Raymond
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Linear Models ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Heterotrimeric G Proteins ◽  
Cellular Functions ◽  
Signaling Specificity ◽  
Intracellular Signals ◽  
Specific Manner

The hormone-receptor-G protein complex transduces extracellular information into intracellular signals that ultimately regulate cellular functions in a highly specific manner. There are hundreds of receptor types that transduce signals through a relatively limited repertoire of heterotrimeric G proteins. Linear models of signaling specificity that require specific and highly selective coupling of hormone to receptor to G protein have proven inadequate to explain how highly particular signals are funneled through the G protein "bottleneck." Recent studies have uncovered a plethora of mechanisms that contribute to signaling specificity. This review focuses on the mechanisms that contribute to specificity in the interactions of receptors with G proteins.

Heterotrimeric G-Protein Signaling in Plants: Conserved and Novel Mechanisms

2019 ◽  
Vol 70 (1) ◽  
pp. 213-238 ◽  
Author(s):  
Sona Pandey
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Stress Responses ◽  
Sequence Information ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Biotic And Abiotic Stress ◽  
Use Efficiency ◽  
Protein Components ◽  
Heterotrimeric G Protein Signaling

Heterotrimeric GTP-binding proteins are key regulators of a multitude of signaling pathways in all eukaryotes. Although the core G-protein components and their basic biochemistries are broadly conserved throughout evolution, the regulatory mechanisms of G proteins seem to have been rewired in plants to meet specific needs. These proteins are currently the focus of intense research in plants due to their involvement in many agronomically important traits, such as seed yield, organ size regulation, biotic and abiotic stress responses, symbiosis, and nitrogen use efficiency. The availability of massive sequence information from a variety of plant species, extensive biochemical data generated over decades, and impressive genetic resources for plant G proteins have made it possible to examine their role, unique properties, and novel regulation. This review focuses on some recent advances in our understanding of the mechanistic details of this critical signaling pathway to enable the precise manipulation and generation of plants to meet future needs.

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 Heterotrimeric G-Protein Signalers and RGSs in Aspergillus fumigatus

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 902
Author(s):  
Hee-Soo Park ◽  
Min-Ju Kim ◽  
Jae-Hyuk Yu ◽  
Kwang-Soo Shin
Keyword(s):  
Aspergillus Fumigatus ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
G Protein ◽  
G Proteins ◽  
Pathogenic Fungus ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Heterotrimeric G Protein ◽  
External Signals

The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting of the α, β, and γ subunits. Regulators of G-protein signaling (RGSs) are the key controllers of G-protein signaling pathways. GPCRs, G-proteins, and RGSs are the primary upstream components of the G-protein signaling pathway, and they are highly conserved in most filamentous fungi, playing diverse roles in biological processes. Recent studies characterized the G-protein signaling components in the opportunistic pathogenic fungus Aspergillus fumigatus. In this review, we have summarized the characteristics and functions of GPCRs, G-proteins, and RGSs, and their regulatory roles in governing fungal growth, asexual development, germination, stress tolerance, and virulence in A. fumigatus.

scholarly journals Regulators of G Protein Signaling Attenuate the G Protein–mediated Inhibition of N-Type Ca Channels

1999 ◽  
Vol 113 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Karim Melliti ◽  
Ulises Meza ◽  
Rory Fisher ◽  
Brett Adams
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Ca Channel ◽  
Protein Signaling ◽  
Ca Channels ◽  
Channel Inhibition ◽  
Kinetics Of ◽  
In Cells

Regulators of G protein signaling (RGS) proteins bind to the α subunits of certain heterotrimeric G proteins and greatly enhance their rate of GTP hydrolysis, thereby determining the time course of interactions among Gα, Gβγ, and their effectors. Voltage-gated N-type Ca channels mediate neurosecretion, and these Ca channels are powerfully inhibited by G proteins. To determine whether RGS proteins could influence Ca channel function, we recorded the activity of N-type Ca channels coexpressed in human embryonic kidney (HEK293) cells with G protein–coupled muscarinic (m2) receptors and various RGS proteins. Coexpression of full-length RGS3T, RGS3, or RGS8 significantly attenuated the magnitude of receptor-mediated Ca channel inhibition. In control cells expressing α1B, α2, and β3 Ca channel subunits and m2 receptors, carbachol (1 μM) inhibited whole-cell currents by ∼80% compared with only ∼55% inhibition in cells also expressing exogenous RGS protein. A similar effect was produced by expression of the conserved core domain of RGS8. The attenuation of Ca current inhibition resulted primarily from a shift in the steady state dose–response relationship to higher agonist concentrations, with the EC50 for carbachol inhibition being ∼18 nM in control cells vs. ∼150 nM in RGS-expressing cells. The kinetics of Ca channel inhibition were also modified by RGS. Thus, in cells expressing RGS3T, the decay of prepulse facilitation was slower, and recovery of Ca channels from inhibition after agonist removal was faster than in control cells. The effects of RGS proteins on Ca channel modulation can be explained by their ability to act as GTPase-accelerating proteins for some Gα subunits. These results suggest that RGS proteins may play important roles in shaping the magnitude and kinetics of physiological events, such as neurosecretion, that involve G protein–modulated Ca channels.

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