scholarly journals A Novel Nuclear Signaling Pathway for Thromboxane A2 Receptors in Oligodendrocytes: Evidence for Signaling Compartmentalization during Differentiation

2008 ◽  
Vol 28 (20) ◽  
pp. 6329-6341 ◽  
Author(s):  
Fozia Mir ◽  
Guy C. Le Breton
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
G Proteins ◽  
Protein Complexes ◽  
Functional Coupling ◽  
Protein Signaling ◽  
Creb Phosphorylation ◽  
Expression Levels ◽  
Nuclear Signaling ◽  
Subcellular Compartmentalization

ABSTRACT The present study investigated G protein expression, localization, and functional coupling to thromboxane A2 receptors (TPRs) during oligodendrocyte (OLG) development. It was found that as OLGs mature, the expression levels of Gq increase while those of G13 decrease. In contrast, the expression levels of Gs, Go, and Gi do not change significantly. Localization studies revealed that Gq, G13, and Gi are present only in the extranuclear compartment, whereas Gs and Go are found in both the extranuclear and the nuclear compartments. Purification of TPR-G protein complexes demonstrated that TPRs couple to both Gq and G13 in the extranuclear compartment but only to Gs in the nuclear compartment. Furthermore, functional analysis revealed that stimulation of nuclear TPR in OLGs stimulates CREB phosphorylation and myelin basic protein transcription and increases survival. Collectively, these results demonstrate that (i) OLGs selectively modulate the expression of certain G proteins during development, (ii) G proteins are differentially localized in OLGs leading to subcellular compartmentalization, (iii) TPRs couple to Gq and G13 in the extranuclear compartment and to Gs only in the nucleus, (iv) mature OLGs have a functional nuclear TPR-Gs signaling pathway, and (v) nuclear TPR signaling can stimulate CREB phosphorylation and myelin gene transcription and increase cell survival. These findings represent a novel paradigm for selective modulation of G protein-coupled receptor-G protein signaling during cell development.

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.

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.

scholarly journals Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli

2011 ◽  
Vol 10 (10) ◽  
pp. 1306-1316 ◽  
Author(s):  
Laura H. Okagaki ◽  
Yina Wang ◽  
Elizabeth R. Ballou ◽  
Teresa R. O'Meara ◽  
Yong-Sun Bahn ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
Pathogenic Fungus ◽  
Cell Formation ◽  
Cell Phenotype ◽  
Protein Signaling ◽  
Human Pathogens ◽  
Morphological Form ◽  
Content Type ◽  
Oxidative Stresses

ABSTRACT The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans . Occurring during the earliest stages of lung infection, titan cells are 5 to 10 times larger than the normal yeast-like cells, thereby resisting engulfment by lung phagocytes and favoring the persistence of infection. These enlarged cells exhibit an altered capsule structure, a thickened cell wall, increased ploidy, and resistance to nitrosative and oxidative stresses. We demonstrate that two G-protein-coupled receptors are important for induction of the titan cell phenotype: the Ste3 a pheromone receptor (in mating type a cells) and the Gpr5 protein. Both receptors control titan cell formation through elements of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. This conserved signaling pathway, in turn, mediates its effect on titan cells through the PKA-regulated Rim101 transcription factor. Additional downstream effectors required for titan cell formation include the G 1 cyclin Pcl103, the Rho104 GTPase, and two GTPase-activating proteins, Gap1 and Cnc1560. These observations support developing models in which the PKA signaling pathway coordinately regulates many virulence-associated phenotypes in diverse human pathogens.

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 Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

Hypertension ◽  
2013 ◽  
Vol 61 (3) ◽  
pp. 655-661 ◽  
Author(s):  
Anne Stine Kvehaugen ◽  
Øyvind Melien ◽  
Oddgeir Lingaas Holmen ◽  
Hannele Laivuori ◽  
Pål Øian ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
G Protein ◽  
G Protein Signaling ◽  
Nucleotide Polymorphisms ◽  
Protein Signaling ◽  
Single Nucleotide
Sign in / Sign up

Export Citation Format

Share Document