scholarly journals Evidence for a Role of the Regulator of G-Protein Signaling Protein CPRGS-1 in Gα Subunit CPG-1-Mediated Regulation of Fungal Virulence, Conidiation, and Hydrophobin Synthesis in the Chestnut Blight Fungus Cryphonectria parasitica

2004 ◽  
Vol 3 (6) ◽  
pp. 1454-1463 ◽  
Author(s):  
Gerrit C. Segers ◽  
Jerome C. Regier ◽  
Donald. L. Nuss
Keyword(s):  
G Protein ◽  
Pathogenic Fungus ◽  
Aerial Mycelium ◽  
Cryphonectria Parasitica ◽  
Chestnut Blight ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Fungal Virulence ◽  
Chestnut Blight Fungus ◽  
Rgs Protein

ABSTRACT We previously reported that the chestnut blight fungus Cryphonectria parasitica expresses at least three G-protein α subunits and that Gα subunit CPG-1 is essential for regulated growth, pigmentation, sporulation, and virulence. We now report the cloning and characterization of a C. parasitica regulator of G-protein signaling (RGS) protein, CPRGS-1. The phylogenetic relationship of CPRGS-1 to orthologs from other fungi was inferred and found to be generally concordant with species relationships based on 18S ribosomal sequences and on morphology. However, Hemiascomycotine RGS branch lengths in particular were longer than for their 18S sequence counterparts, which correlates with functional diversification in the signaling pathway. Deletion of cprgs-1 resulted in reduced growth, sparse aerial mycelium, and loss of pigmentation, sporulation, and virulence. Disruption of cprgs-1 was also accompanied by a severe posttranscriptional reduction in accumulation of CPG-1 and Gβ subunit CPGB-1 and severely reduced expression of the hydrophobin-encoding gene cryparin. The changes in phenotype, cryparin expression, and CPGB-1 accumulation resulting from cprgs-1 gene deletion were also observed in a strain containing a mutationally activated copy of CPG-1 but not in strains containing constitutively activated mutant alleles of the other two identified Gα subunits, CPG-2 and CPG-3. Furthermore, cprgs-1 transcript levels were increased in the activated CPG-1 strain but were unaltered in activated CPG-2 and CPG-3 strains. The results strongly suggest that CPRGS-1 is involved in regulation of Gα subunit CPG-1-mediated signaling and establish a role for a RGS protein in the modulation of virulence, conidiation, and hydrophobin synthesis in a plant pathogenic fungus.

scholarly journals Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of RGS17 and Problematic Chemical Substructures

2018 ◽  
Vol 23 (4) ◽  
pp. 363-374 ◽  
Author(s):  
Christopher R. Bodle ◽  
Josephine H. Schamp ◽  
Joseph B. O’Brien ◽  
Michael P. Hayes ◽  
Meng Wu ◽  
...  
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
High Throughput Screening ◽  
Biochemical Characterization ◽  
Parent Compound ◽  
Receptor Activation ◽  
G Protein Signaling ◽  
Conservation Of Resources ◽  
Protein Signaling ◽  
Rgs Protein

Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein–coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers. A screen of over 60,000 small molecules led to the identification of five hit compounds that inhibit the RGS17-Gαo protein-protein interaction. Chemical and biochemical characterization demonstrated that three of these hits inhibited the interaction through the decomposition of parent compound into reactive products under normal chemical library storage/usage conditions. Compound substructures susceptible to decomposition are reported and the decomposition process characterized, adding to the armamentarium of tools available to the screening field, allowing for the conservation of resources in follow-up efforts and more efficient identification of potentially decomposed compounds. Finally, analogues of one hit compound were tested, and the results establish the first ever structure-activity relationship (SAR) profile for a small-molecule inhibitor of RGS17.

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 Gα and regulator of G-protein signaling (RGS) protein pairs maintain functional compatibility and conserved interaction interfaces throughout evolution despite frequent loss of RGS proteins in plants

2016 ◽  
Vol 216 (2) ◽  
pp. 562-575 ◽  
Author(s):  
Dieter Hackenberg ◽  
Michael R. McKain ◽  
Soon Goo Lee ◽  
Swarup Roy Choudhury ◽  
Tyler McCann ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Rgs Protein

scholarly journals Multiple RGS proteins alter neural G protein signaling to allow C. elegans to rapidly change behavior when fed

2000 ◽  
Vol 14 (16) ◽  
pp. 2003-2014 ◽  
Author(s):  
Meng-Qiu Dong ◽  
Daniel Chase ◽  
Georgia A. Patikoglou ◽  
Michael R. Koelle
Keyword(s):  
G Protein ◽  
Egg Laying ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
C Elegans ◽  
Change Behavior ◽  
Rgs Protein ◽  
Heterotrimeric G Protein Signaling

Regulators of G protein signaling (RGS proteins) inhibit heterotrimeric G protein signaling by activating G protein GTPase activity. Many mammalian RGS proteins are expressed in the brain and can act in vitro on the neural G protein Go, but the biological purpose of this multiplicity of regulators is not clear. We have analyzed all 13 RGS genes in Caenorhabditis elegans and found that three of them influence the aspect of egg-laying behavior controlled by Go signaling. A previously studied RGS protein, EGL-10, affects egg laying under all conditions tested. The other two RGS proteins, RGS-1 and RGS-2, act as Go GTPase activators in vitro but, unlike EGL-10, they do not strongly affect egg laying when worms are allowed to feed constantly. However, rgs-1; rgs-2double mutants fail to rapidly induce egg-laying behavior when refed after starvation. Thus EGL-10 sets baseline levels of signaling, while RGS-1 and RGS-2 appear to redundantly alter signaling to cause appropriate behavioral responses to food.

Pka, Ras and RGS Protein Interactions Regulate Activity of AflR, a Zn(II)2Cys6 Transcription Factor in Aspergillus nidulans

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1095-1104
Author(s):  
Kiminori Shimizu ◽  
Julie K Hicks ◽  
Tzu-Pi Huang ◽  
Nancy P Keller
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Aspergillus Nidulans ◽  
G Protein ◽  
Protein Interactions ◽  
Transcriptional Control ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Rgs Protein ◽  
Post Transcriptional Regulation

Abstract Sterigmatocystin (ST) is a carcinogenic polyketide produced by several filamentous fungi including Aspergillus nidulans. Expression of ST biosynthetic genes (stc genes) requires activity of a Zn(II)2Cys6 transcription factor, AflR. aflR is transcriptionally and post-transcriptionally regulated by a G-protein/cAMP/protein kinase A (PkaA) signaling pathway involving FlbA, an RGS (regulator of G-protein signaling) protein. Prior genetic data showed that FlbA transcriptional regulation of aflR was PkaA dependent. Here we show that mutation of three PkaA phosphorylation sites in AflR allows resumption of stc expression in an overexpression pkaA background but does not remediate stc expression in a ΔflbA background. This demonstrates negative regulation of AflR activity by phosphorylation and shows that FlbA post-transcriptional regulation of aflR is PkaA independent. AflR nucleocytoplasmic location further supports PkaA-independent regulation of AflR by FlbA. GFP-tagged AflR is localized to the cytoplasm when pkaA is overexpressed but nuclearly located in a ΔflbA background. aflR is also transcriptionally and post-transcriptionally regulated by RasA. RasA transcriptional control of aflR is PkaA independent but RasA post-transcriptional control of AflR is partially mediated by PkaA.

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