ArticleCellular signalling2012
Protease-activated receptor 1 (PAR1) coupling to G(q/11) but not to G(i/o) or G(12/13) is mediated by discrete amino acids within the receptor second intracellular loop.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- A massively parallel reporter assay library to screen short synthetic promoters in mammalian cells.Nature communications · 2024Article
- Light-sensitive CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- PAR1-mediated Non-periodical Synchronized Calcium Oscillations in Human Mesangial Cells.Function (Oxford, England) · 2024Article
- Gq Signaling in Autophagy Control: Between Chemical and Mechanical Cues.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Platelet Signaling and Disease: Targeted Therapy for Thrombosis and Other Related Diseases.Pharmacological reviews · 2018Review
- Genetic Variant in Human PAR (Protease-Activated Receptor) 4 Enhances Thrombus Formation Resulting in Resistance to Antiplatelet Therapeutics.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Activation of astrocytic PAR1 receptors in the rat nucleus of the solitary tract regulates breathing through modulation of presynaptic TRPV1.The Journal of physiology · 2018Article
- Neuro-Immune Hemostasis: Homeostasis and Diseases in the Central Nervous System.Frontiers in cellular neuroscience · 2018Review
- Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.International journal of molecular sciences · 2017Review
- PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology.Scientific reports · 2017Article
- Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1.Scientific reports · 2016Article
- TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells.Oncotarget · 2016Article
- Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases.European journal of pharmacology · 2015Review
- N-linked glycosylation of protease-activated receptor-1 at extracellular loop 2 regulates G-protein signaling bias.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar.Blood · 2015Article
- Thrombin regulation of synaptic transmission and plasticity: implications for health and disease.Frontiers in cellular neuroscience · 2015Review
- Differential signaling by protease-activated receptors: implications for therapeutic targeting.International journal of molecular sciences · 2014Review
- Homogeneous time-resolved fluorescence-based assay to monitor extracellular signal-regulated kinase signaling in a high-throughput format.Frontiers in endocrinology · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Protease-activated receptor 1 (PAR1) is an unusual GPCR that interacts with multiple G protein subfamilies (G(q/11), G(i/o), and G(12/13)) and their linked signaling pathways to regulate a broad range of pathophysiological processes. However, the molecular mechanisms whereby PAR1 interacts with multiple G proteins are not well understood. Whether PAR1 interacts with various G proteins at the same, different, or overlapping binding sites is not known. Here we investigated the functional and specific binding interactions between PAR1 and representative members of the G(q/11), G(i/o), and G(12/13) subfamilies. We report that G(q/11) physically and functionally interacts with specific amino acids within the second intracellular (i2) loop of PAR1. We identified five amino acids within the PAR1 i2 loop that, when mutated individually, each markedly reduced PAR1 activation of linked inositol phosphate formation in transfected COS-7 cells (functional PAR1-null cells). Among these mutations, only R205A completely abolished direct G(q/11) binding to PAR1 and also PAR1-directed inositol phosphate and calcium mobilization in COS-7 cells and PAR1-/- primary astrocytes. In stark contrast, none of the PAR1 i2 loop mutations disrupted direct PAR1 binding to either G(o) or G(12), or their functional coupling to linked pertussis toxin-sensitive ERK phosphorylation and C3 toxin-sensitive Rho activation, respectively. In astrocytes, our findings suggest that PAR1-directed calcium signaling involves a newly appreciated G(q/11)-PLCε pathway. In summary, we have identified key molecular determinants for PAR1 interactions with G(q/11), and our findings support a model where G(q/11), G(i/o) or G(12/13) each bind to distinct sites within the cytoplasmic regions of PAR1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.