scholarly journals A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

2013 ◽  
Vol 49 (1) ◽  
pp. 94-108 ◽  
Author(s):  
Jose P. Vaqué ◽  
Robert T. Dorsam ◽  
Xiaodong Feng ◽  
Ramiro Iglesias-Bartolome ◽  
David J. Forsthoefel ◽  
...  
Keyword(s):  
G Protein ◽  
Rho Gtpase ◽  
Rnai Screen ◽  
G Protein Coupled Receptors ◽  
Genome Wide ◽  
A Genome ◽  
G Protein Coupled ◽  
Mitogenic Signals

scholarly journals Identification of the C3a Receptor (C3AR1) as the Target of the VGF-derived Peptide TLQP-21 in Rodent Cells

2013 ◽  
Vol 288 (38) ◽  
pp. 27434-27443 ◽  
Author(s):  
Sebastien Hannedouche ◽  
Valerie Beck ◽  
Juliet Leighton-Davies ◽  
Martin Beibel ◽  
Guglielmo Roma ◽  
...  
Keyword(s):  
G Protein ◽  
Cellular Response ◽  
G Protein Coupled Receptors ◽  
Proteolytic Processing ◽  
Rodent Models ◽  
Cellular Functions ◽  
Genome Wide ◽  
Response To Stress ◽  
G Protein Coupled ◽  
Human Receptor

TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation, and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This study describes the use of a series of studies that show G protein-coupled receptor-mediated biological activity of TLQP-21 signaling in CHO-K1 cells. Unbiased genome-wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible G protein-coupled receptors bringing about this activity. Further experiments using a series of defined receptor antagonists and siRNAs led to the identification of complement C3a receptor-1 (C3AR1) as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signaling to pertussis toxin is consistent with the known signaling pathway of C3AR1. The binding of TLQP-21 to C3AR1 not only has effects on signaling but also modulates cellular functions, as TLQP-21 was shown to have a role in directing migration of mouse RAW264.7 cells.

Rho GTPase-dependent transformation by G protein-coupled receptors

Oncogene ◽  
2001 ◽  
Vol 20 (13) ◽  
pp. 1547-1555 ◽  
Author(s):  
Ian P Whitehead ◽  
Irene E Zohn ◽  
Channing J Der
Keyword(s):  
G Protein ◽  
Rho Gtpase ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

Genome-wide prediction of G protein-coupled receptors in Verticillium spp.

2010 ◽  
Vol 114 (4) ◽  
pp. 359-368 ◽  
Author(s):  
Hongxia Zheng ◽  
Lei Zhou ◽  
Tonghai Dou ◽  
Xiaotian Han ◽  
Yanyan Cai ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Genome Wide ◽  
G Protein Coupled

scholarly journals The G protein–coupled receptor GPR31 promotes membrane association of KRAS

2017 ◽  
Vol 216 (8) ◽  
pp. 2329-2338 ◽  
Author(s):  
Nicole Fehrenbacher ◽  
Israel Tojal da Silva ◽  
Craig Ramirez ◽  
Yong Zhou ◽  
Kwang-Jin Cho ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
G Protein ◽  
Secretory Pathway ◽  
Membrane Association ◽  
G Protein Coupled Receptor ◽  
Genome Wide ◽  
A Genome ◽  
G Protein Coupled

The product of the KRAS oncogene, KRAS4B, promotes tumor growth when associated with the plasma membrane (PM). PM association is mediated, in part, by farnesylation of KRAS4B, but trafficking of nascent KRAS4B to the PM is incompletely understood. We performed a genome-wide screen to identify genes required for KRAS4B membrane association and identified a G protein–coupled receptor, GPR31. GPR31 associated with KRAS4B on cellular membranes in a farnesylation-dependent fashion, and retention of GPR31 on the endoplasmic reticulum inhibited delivery of KRAS4B to the PM. Silencing of GPR31 expression partially mislocalized KRAS4B, slowed the growth of KRAS-dependent tumor cells, and blocked KRAS-stimulated macropinocytosis. Our data suggest that GPR31 acts as a secretory pathway chaperone for KRAS4B.

scholarly journals Orphan G Protein Coupled Receptors in Affective Disorders

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 694 ◽  
Author(s):  
Lyndsay R. Watkins ◽  
Cesare Orlandi
Keyword(s):  
G Protein ◽  
Animal Studies ◽  
Association Studies ◽  
G Protein Coupled Receptors ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Pharmacological Targets ◽  
The Central Nervous System ◽  
Orphan Gpcrs ◽  
G Protein Coupled

G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B.

scholarly journals R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ramin Dubey ◽  
Peter van Kerkhof ◽  
Ingrid Jordens ◽  
Tomas Malinauskas ◽  
Ganesh V Pusapati ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Cultured Cells ◽  
Heparan Sulfate Proteoglycans ◽  
G Protein Coupled Receptors ◽  
Binding Domains ◽  
Genome Wide ◽  
A Genome ◽  
G Protein Coupled ◽  
In Cells

R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 and 3 potentiate WNT/β-catenin signaling in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 and 6 (Lebensohn and Rohatgi, 2018). We now show that heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis and ligand engineering. Mutations in RSPO3 residues predicted to contact HSPGs impair its signaling capacity. Conversely, the HSPG-binding domains of RSPO3 can be entirely replaced with an antibody that recognizes heparan sulfate (HS) chains attached to multiple HSPGs without diminishing WNT-potentiating activity in cultured cells and intestinal organoids. A genome-wide screen for mediators of RSPO3 signaling in cells lacking LGRs 4, 5 and 6 failed to reveal other receptors. We conclude that HSPGs are RSPO co-receptors that potentiate WNT signaling in the presence and absence of LGRs.

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