ArticleThe Journal of biological chemistry2013
Carboxypeptidase M is a positive allosteric modulator of the kinin B1 receptor.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Bradykinin B2 Receptor Signaling Increases Glucose Uptake and Oxidation: Evidence and Open Questions.Frontiers in pharmacology · 2020Pooled it
- Plasma proteomic signatures of biological aging and metabolic dysfunction-associated steatotic liver disease risk: a prospective cohort study.Hepatology international · 2026Article
- In vivo measurement of an Apelin gradient with a genetically encoded APLNR conformation biosensor.Nature communications · 2025Article
- Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy.Journal of clinical medicine · 2023Article
- Investigating G-protein coupled receptor signalling with light-emitting biosensors.Frontiers in physiology · 2023Review
- A comprehensive review on current understanding of bradykinin in COVID-19 and inflammatory diseases.Molecular biology reports · 2022Review
- Genetically encoded fluorescent biosensors for GPCR research.Frontiers in cell and developmental biology · 2022Review
- Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart.Physiological reports · 2021Article
- Substrate Specificity and Structural Modeling of Human Carboxypeptidase Z: A Unique Protease with a Frizzled-Like Domain.International journal of molecular sciences · 2020Article
- Angiotensin-Converting Enzyme Inhibitor Protects Against Cisplatin Nephrotoxicity by Modulating Kinin B1 Receptor Expression and Aminopeptidase P Activity in Mice.Frontiers in molecular biosciences · 2020Article
- The kinin BInflammopharmacology · 2019Article
- Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.Occupational and environmental medicine · 2019Article
- Substrate specificity of human metallocarboxypeptidase D: Comparison of the two active carboxypeptidase domains.PloS one · 2017Article
- Kininase 1 As a Preclinical Therapeutic Target for Kinin BFrontiers in pharmacology · 2017Article
- HAE Pathophysiology and Underlying Mechanisms.Clinical reviews in allergy & immunology · 2016Review
- Optical probes based on G protein-coupled receptors - added work or added value?British journal of pharmacology · 2016Review
- The effect of kinin B1 receptor on chronic itching sensitization.Molecular pain · 2015Article
- Downregulation of kinin B1 receptor function by B2 receptor heterodimerization and signaling.Cellular signalling · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ligand binding to extracellular domains of G protein-coupled receptors can result in novel and nuanced allosteric effects on receptor signaling. We previously showed that the protein-protein interaction of carboxypeptidase M (CPM) and kinin B1 receptor (B1R) enhances B1R signaling in two ways; 1) kinin binding to CPM causes a conformational activation of the B1R, and 2) CPM-generated des-Arg-kinin agonist is efficiently delivered to the B1R. Here, we show CPM is also a positive allosteric modulator of B1R signaling to its agonist, des-Arg(10)-kallidin (DAKD). In HEK cells stably transfected with B1R, co-expression of CPM enhanced DAKD-stimulated increases in intracellular Ca(2+) or phosphoinositide turnover by a leftward shift of the dose-response curve without changing the maximum. CPM increased B1R affinity for DAKD by ∼5-fold but had no effect on basal B1R-dependent phosphoinositide turnover. Soluble, recombinant CPM bound to HEK cells expressing B1Rs without stimulating receptor signaling. CPM positive allosteric action was independent of enzyme activity but depended on interaction of its C-terminal domain with the B1R extracellular loop 2. Disruption of the CPM/B1R interaction or knockdown of CPM in cytokine-treated primary human endothelial cells inhibited the allosteric enhancement of CPM on B1R DAKD binding or ERK1/2 activation. CPM also enhanced the DAKD-induced B1R conformational change as detected by increased intramolecular fluorescence or bioluminescence resonance energy transfer. Thus, CPM binding to extracellular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption of this interaction could provide a novel therapeutic approach to reduce pathological B1R signaling.
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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.