ArticleCell communication and signaling : CCS2020
Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Identification of Hub Neutrophil Coexpressed Genes in Acute PancreatitisEndocrine, metabolic & immune disorders drug targets · 2026Article
- Unveiling the mechanisms of CEBPD-orchestrated TAM polarization through RGS2/PAR2 pathway and its impact on ICB efficacy in clear cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Discovery of RGS2-FBXO44 interaction inhibitors using a cell-based NanoBit assay.Molecular pharmacology · 2025Article
- Urinary exosomal miR-320b as a biomarker of tubular atrophy/interstitial fibrosis in IgA nephropathy patients.American journal of translational research · 2025Article
- Ophiopogonin D' inhibited tumour growth and metastasis of anaplastic thyroid cancer by modulating JUN/RGS4 signalling.Journal of cellular and molecular medicine · 2024Article
- RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms.The Journal of biological chemistry · 2024Article
- Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.Nature communications · 2024Article
- Regulators of G-Protein Signaling (RGS) in Sporadic and Colitis-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- Function and regulation of RGS family members in solid tumours: a comprehensive review.Cell communication and signaling : CCS · 2023Review
- RGS proteins and their roles in cancer: friend or foe?Cancer cell international · 2023Review
- A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia.Biomedicines · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- The Potential Role of R4 Regulators of G Protein Signaling (RGS) Proteins in Type 2 Diabetes Mellitus.Cells · 2022Review
- Protease Activated Receptors and Arthritis.International journal of molecular sciences · 2021Review
- Acute and 28-days subacute toxicity studies of Gαq-RGS2 signaling inhibitor.Laboratory animal research · 2021Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21.Cancer science · 2021Article
- Host-Parasite Interaction of Atlantic salmon (Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProtease-activated receptor 4 (PAR4) is a seven transmembrane G-protein coupled receptor (GPCR) activated by endogenous proteases, such as thrombin. PAR4 is involved in various pathophysiologies including cancer, inflammation, pain, and thrombosis. Although regulators of G-protein signaling (RGS) are known to modulate GPCR/Gα-mediated pathways, their specific effects on PAR4 are not fully understood at present. We previously reported that RGS proteins attenuate PAR1- and PAR2-mediated signaling through interactions with these receptors in conjunction with distinct Gα subunits.
methodsWe employed a bioluminescence resonance energy transfer technique and confocal microscopy to examine potential interactions among PAR4, RGS, and Gα subunits. The inhibitory effects of RGS proteins on PAR4-mediated downstream signaling and cancer progression were additionally investigated by using several assays including ERK phosphorylation, calcium mobilization, RhoA activity, cancer cell proliferation, and related gene expression.
resultsIn live cells, RGS2 interacts with PAR4 in the presence of Gα
conclusionsRGS2 and RGS4 forms ternary complex with PAR4 in Gα-dependent manner and inhibits its downstream signaling. Our findings support a novel physiological function of RGS2 and RGS4 as inhibitors of PAR4-mediated signaling through selective PAR4/RGS/Gα coupling. Video Abstract.
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