scholarly journals Cutting Edge: A Critical Role for the G Protein-Coupled Receptor mFPR2 in Airway Inflammation and Immune Responses

2010 ◽  
Vol 184 (7) ◽  
pp. 3331-3335 ◽  
Author(s):  
Keqiang Chen ◽  
Yingying Le ◽  
Ying Liu ◽  
Wanghua Gong ◽  
Guoguang Ying ◽  
...  
Keyword(s):  
Immune Responses ◽  
Airway Inflammation ◽  
G Protein ◽  
Critical Role ◽  
Cutting Edge ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Cutting Edge: Identification of the Orphan Receptor G-Protein-Coupled Receptor 2 as CCR10, a Specific Receptor for the Chemokine ESkine

2000 ◽  
Vol 164 (7) ◽  
pp. 3460-3464 ◽  
Author(s):  
David I. Jarmin ◽  
Miriam Rits ◽  
Dalena Bota ◽  
Norma P. Gerard ◽  
Gerard J. Graham ◽  
...  
Keyword(s):  
G Protein ◽  
Cutting Edge ◽  
Orphan Receptor ◽  
Specific Receptor ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses

Immunity ◽  
2009 ◽  
Vol 31 (2) ◽  
pp. 259-269 ◽  
Author(s):  
Dominique Gatto ◽  
Didrik Paus ◽  
Antony Basten ◽  
Charles R. Mackay ◽  
Robert Brink
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
G Protein Coupled

scholarly journals Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Alexandra Anderson ◽  
Yee Lian Chew ◽  
William Schafer ◽  
Rachel McMullan
Keyword(s):  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled Receptor ◽  
Content Type ◽  
C Elegans ◽  
Host Immune Responses ◽  
Pathogen Clearance ◽  
G Protein Coupled

ABSTRACT G protein-coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. While it has become well established that the nematode worm Caenorhabditis elegans triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which C. elegans recognizes these pathogens have remained somewhat more elusive. C. elegans G protein-coupled receptors have been implicated in recognizing pathogen-associated damage and activating downstream host immune responses. Here we identify and characterize a novel G protein-coupled receptor required to regulate the C. elegans response to infection with Microbacterium nematophilum. We show that this receptor, which we designate pathogen clearance-defective receptor 1 (PCDR-1), is required for efficient pathogen clearance following infection. PCDR-1 acts upstream of multiple G proteins, including the C. elegans Gαq ortholog, EGL-30, in rectal epithelial cells to promote pathogen clearance via a novel mechanism.

scholarly journals Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

2015 ◽  
Vol 89 (19) ◽  
pp. 9932-9938 ◽  
Author(s):  
Han Cheng ◽  
Calli M. Lear-Rooney ◽  
Lisa Johansen ◽  
Elizabeth Varhegyi ◽  
Zheng W. Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
G Protein ◽  
High Mortality ◽  
Ebola Virus ◽  
Critical Role ◽  
Marburg Virus ◽  
Severe Illness ◽  
G Protein Coupled Receptor ◽  
Chemical Library ◽  
G Protein Coupled

ABSTRACTFiloviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy.IMPORTANCEInfection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy.

scholarly journals Acute loss of Cell–Cell Communication Caused by G Protein–coupled Receptors: A Critical Role for c-Src

1998 ◽  
Vol 140 (5) ◽  
pp. 1199-1209 ◽  
Author(s):  
Friso R. Postma ◽  
Trudi Hengeveld ◽  
Jacqueline Alblas ◽  
Ben N.G. Giepmans ◽  
Gerben C.M. Zondag ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gap Junction ◽  
G Protein ◽  
Critical Role ◽  
Cell Communication ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled Receptor ◽  
Junction Protein ◽  
G Protein Coupled ◽  
Cell Cell

Gap junctions mediate cell–cell communication in almost all tissues, but little is known about their regulation by physiological stimuli. Using a novel single-electrode technique, together with dye coupling studies, we show that in cells expressing gap junction protein connexin43, cell–cell communication is rapidly disrupted by G protein–coupled receptor agonists, notably lysophosphatidic acid, thrombin, and neuropeptides. In the continuous presence of agonist, junctional communication fully recovers within 1–2 h of receptor stimulation. In contrast, a desensitization-defective G protein–coupled receptor mediates prolonged uncoupling, indicating that recovery of communication is controlled, at least in part, by receptor desensitization. Agonist-induced gap junction closure consistently follows inositol lipid breakdown and membrane depolarization and coincides with Rho-mediated cytoskeletal remodeling. However, we find that gap junction closure is independent of Ca2+, protein kinase C, mitogen-activated protein kinase, or membrane potential, and requires neither Rho nor Ras activation. Gap junction closure is prevented by tyrphostins, by dominant-negative c-Src, and in Src-deficient cells. Thus, G protein–coupled receptors use a Src tyrosine kinase pathway to transiently inhibit connexin43-based cell–cell communication.

scholarly journals Critical Role for the Second Extracellular Loop in the Binding of Both Orthosteric and Allosteric G Protein-coupled Receptor Ligands

2007 ◽  
Vol 282 (35) ◽  
pp. 25677-25686 ◽  
Author(s):  
Vimesh A. Avlani ◽  
Karen J. Gregory ◽  
Craig J. Morton ◽  
Michael W. Parker ◽  
Patrick M. Sexton ◽  
...  
Keyword(s):  
G Protein ◽  
Critical Role ◽  
Extracellular Loop ◽  
Receptor Ligands ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Estrogen Signaling Characteristics of Atlantic Croaker G Protein-Coupled Receptor 30 (GPR30) and Evidence It Is Involved in Maintenance of Oocyte Meiotic Arrest

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3410-3426 ◽  
Author(s):  
Yefei Pang ◽  
Jing Dong ◽  
Peter Thomas
Keyword(s):  
G Protein ◽  
Plasma Membranes ◽  
Critical Role ◽  
Hek293 Cells ◽  
Atlantic Croaker ◽  
Estrogen Signaling ◽  
G Protein Coupled Receptor ◽  
Meiotic Arrest ◽  
Transfected Cells ◽  
G Protein Coupled

Human G protein-coupled receptor 30 (GPR30) mediates estradiol-17β (E2) activation of adenylyl cyclase in breast cancer cells and displays E2 binding typical of membrane estrogen receptors (mERs). We identified a mER in Atlantic croaker ovaries with characteristics similar to those of human GPR30. To confirm the proposed role of GPR30 as a mER in this distantly related vertebrate group, we cloned GPR30 from croaker ovaries and examined its distribution, steroid binding, and signaling characteristics. Western blot analysis showed the GPR30 protein (∼40 kDa) is expressed on the plasma membranes of croaker oocytes and HEK293 cells stably transfected with GPR30 cDNA. Plasma membranes prepared from croaker GPR30-transfected cells displayed high-affinity, limited-capacity, and displaceable binding specific for estrogens, characteristic of mERs. Consistent with previous findings with human GPR30, estrogen treatment of plasma membranes from both croaker ovaries and GPR30-transfected cells caused activation of a stimulatory G protein (Gs) resulting in increased cAMP production. Treatment with E2 as well as G-1, a specific GPR30 ligand, significantly reduced both spontaneous and progestin-induced maturation of both croaker and zebrafish oocytes in vitro, suggesting a possible involvement of GPR30 in maintaining oocyte meiotic arrest in these species. Injection of antisense oligonucleotides to GPR30 into zebrafish oocytes blocked the inhibitory effects of estrogen on oocyte maturation, confirming a role for GPR30 in the control of meiotic arrest. These findings further support our previous suggestion that GPR30 is a vertebrate mER. In addition, the results suggest GRP30 may play a critical role in regulating reentry into the meiotic cell cycle in fish oocytes.

scholarly journals Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses

2006 ◽  
Vol 15 (10) ◽  
pp. 1667-1679 ◽  
Author(s):  
Ville Pulkkinen ◽  
Marja-Leena Majuri ◽  
Guoying Wang ◽  
Päivi Holopainen ◽  
Yasushi Obase ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Neuropeptide S ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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