September 2022 "G-protein-coupled receptors (GPCRs) are involved in a wide array of physiological and Here, we find that protease-activated receptor 4 (PAR4) unexpectedly acts as a potent oncogene, inducing β-catenin stability and transcriptional activity. β-catenin stability and transcriptional activity. following PAR4 activation, in contrast to wt β-catenin.

October 2022 "Protease activated receptors (PARs) are among the first receptors shown to transactivate other receptors: noticeably, these interactions are not limited to members of the same family, but involve receptors as diverse as receptor kinases, prostanoid receptors, purinergic receptors and ionic channels In this review, we will focus on the evidence for PAR interactions with members of their own family, as well as with other types of receptors.

August 2022 "As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-Gi Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor ) signaling and provide insights into the diversity of G protein coupling."

September 2022 "Introduction Protease activated receptors 1 (PAR1) and 4 (PAR4) agonists are used to study platelet activation. Data on platelet activation are extrapolated across experimental settings. C1-inhibitor (C1INH) is a protease inhibitor present in plasma but not in isolated platelet suspensions Here we show that C1INH affects platelet activation through PAR1 and PAR4 agonists.

September 2022 To probe the activation mechanism of the Delta opioid receptor by an agonist ADL5859 started from inactive conformation using molecular dynamic simulations "The δ-opioid receptor (DOR) is a critical inactive DOR and multiple microsecond molecular dynamic (MD) simulations were conducted to probe the activation While the receptor with the crystal ligand (i.e. antagonist naltrindole) maintained the inactive conformation in all three independent simulations, the receptor with ADL5859 was adopting toward the active conformation

October 2022 Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to inverse agonism "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating The cholesterol did not interfere with the agonist-induced activation of monomeric β2-AR, unlike the

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed this work, molecular docking screens for allosteric modulators targeting the metabotropic glutamate receptor The mGlu5 receptor is activated by the main excitatory neurotransmitter of the nervous central system , L-glutamate, and mGlu5 receptor activity can be allosterically modulated by negative or positive allosteric The mGlu5 receptor is a promising target for the treatment of psychiatric and neurodegenerative diseases

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound

Prokineticins (PKs) exert their biological functions through the activation of the G protein-coupled receptors (GPCRs) prokineticin receptor 1 and 2 (PKR1, 2), and mutations in the PK2 and PKR2 genes are this protein is able to enhance the activation of the ERK1/2 (extracellular signal-regulated kinase 1 The whey acidic protein domain (WAP) is necessary for this modulatory activity, although data from GST of the receptor by PK2.

chondrocyte/chondroprogenitor Ca2+ signaling has been attempted through mechanical and/or pharmacological activation signaling transducers; however, such approaches can lack specificity and/or precision regarding Ca2+ activation One such platform is the chemogenetic DREADD (designer receptor exclusively activated by designer drugs ) hM3Dq, which activates [Ca2+]i signaling via the Gαq-PLCβ-IP3-ER pathway upon clozapine N-oxide (CNO This study demonstrated Gαq-G-protein coupled receptor (GPCR)-mediated [Ca2+]i signaling involvement

We find that PFC astrocytes express receptors for dopamine but are unresponsive through the Gs/Gi-cAMP calcium signals in PFC astrocytes are time locked to dopamine release and are mediated by α1-adrenergic receptors Thus, we identify astrocytes as active players in dopaminergic signaling in the PFC, contributing to PFC function though neuromodulator receptor crosstalk."

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 receptor at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity in complex with antagonists and agonists, our structure with S1P5-inverse agonist sheds light on the activation

October 2022 Activation of GPR183 by 7 α,25-Dihydroxycholesterol Induces Behavioral Hypersensitivity through Mitogen-Activated Protein Kinase and Nuclear Factor- κ B "Emerging evidence implicates the G-protein coupled receptor (GPCR) GPR183 in the development of neuropathic pain. tissues harvested at the time of peak hypersensitivity implicate potential contributions of mitogen-activated that the development of 7α,25-OHC/GPR183-induced mechano-allodynia was associated with significant activation

cannabinoid receptors, CB1 and CB2. Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized representing a potentially significant pathway which plays a role in the control of skeletal muscular activities The part played by CB1 receptor activation or inhibition with respect to these functions and relevant function and disease processes.

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid The primary analgesic target of opioids is the μ-opioid receptor (MOR). found that MOR alone could not stimulate PLC, but rather required a coincident signal from a Gq coupled receptor These data support a model where Gq and Gβγ-dependent signaling cooperatively regulate PLC activation

September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF , even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated

That precursor is inactive, but proteases from the coagulation and fibrinolytic cascades, as well as from inflammatory reactions, process the C-terminus of chemerin to first activate it and then subsequently Chemerin can signal via two G protein-coupled receptors, chem1 and chem2, as well as be bound to a third non-signaling receptor, CCRL2. in regulating the activation and inactivation of chemerin.

October 2022 "While the role of G-protein-coupled receptors (GPCR) in cancer is acknowledged, their underlying Protease-activated receptors (PAR), a subgroup of GPCRs, form a family of four members (PAR1-4) centrally In addition to PH-Akt/PKB association, other PH-containing signal proteins such as Gab1 and Sos1 also AYPGKF peptide ligand activation of PAR4 induces EGF receptor (EGFR) Tyr-phosphorylation, effectively We propose that Pc(4-4) may serve as a powerful drug not only toward PAR-expressing tumors but also for

August 2022 "Background: Activation of signaling effectors by G-protein coupled receptors (GPCRs) depends Although studies have focused on the G-protein signaling state, the mechanism for β-arrestin signaling

November 2022 "Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating The cholesterol did not interfere with the agonist-induced activation of monomeric β2-AR, unlike the

activation, G protein interactions, signaling dynamics, and signal termination, highlighting the importance of studying their role in the activation of GPCRs2. β-arrestins are cytosolic proteins that translocate to the plasma membrane upon GPCR activation, then regulate trigger receptor internalization via interaction Transient interaction with the receptor catalyzes β-arrestin activation, including β-arrestin inter-domain Plasma membrane preassociation drives β-arrestin coupling to receptors and activation.

October 2022 "The canonical model for G protein-coupled receptors (GPCRs) activation assumes that stimulation In this model, GPCR signaling is turned-off by receptor phosphorylation via GPCR kinases (GRKs) and subsequent recruitment of β-arrestins, resulting in receptor internalization into endosomes. Internalized receptors can then recycle back to the cell surface or be trafficked to lysosomes for degradation This is the case for the parathyroid hormone (PTH) type 1 receptor (PTHR), which engages on sustained

September 2022 PLC-IP3-ORAI pathway participates in the activation of the MRGPRB2 receptor in mouse peritoneal mast cells "A novel mast cell-specific G-protein-coupled receptor (GPCR), known as Mas-related G protein-coupled receptor-B2 (MRGPRB2), plays important roles in immune response. However, the opening of ion channels mediated by MRGPRB2 activation remains unclear. The voltage-dependent current induced by MRGPRB2 was inhibited by calcium-activated chlorine channel

receptors (chemokine receptors, CKRs) and glycosaminoglycans (GAGs) to regulate the movement of leukocytes In humans there are approximately 45 chemokines, 19 chemotactic or G-protein coupled chemokine receptors (CKRs) that signal via Gαi and 4 official atypical chemokine receptors (ACKRs) which engage in ligand CCR2 is an example of a dual-function receptor that directly regulates both cell migration and scavenging , which is a different mechanism from what has been established for other chemokine scavenger receptors

The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities

October 2022 Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1β and CXCL2 which are vital for

Most acquired genes are transmembrane proteins and cytokines, such as viral G protein-coupled receptors (vGPCRs), chemokines, and chemokine-binding proteins. These include receptors from human cytomegalovirus, which encodes four vGPCRs: US27, US28, UL33, and UL78; human herpesvirus 6 and 7 with two receptors: U12 and U51; Epstein-Barr virus with one: BILF1; ligand binding, signaling, and structures of the vGPCRs in light of robust differences from endogenous receptors

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Likewise, the relative importance of receptor activation state and ligand function differences have also are more likely to produce substantial improvements for other pairings of receptor activation state