ArticleThe Journal of biological chemistry2009
Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Broadening the View: Substance P and Its Metabolism in Pruritus-Related Diseases.The Journal of dermatology · 2026Review
- Therapeutic antagonism of the neurokinin 1 receptor in endosomes provides sustained pain relief.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Susceptibility ofFrontiers in pediatrics · 2022Article
- A Novel Mechanism of Endoplasmic Reticulum Stress- and c-Myc-Degradation-Mediated Therapeutic Benefits of Antineurokinin-1 Receptor Drugs in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Comparative Cell Surface Proteomic Analysis of the Primary Human T Cell and Monocyte Responses to Type I Interferon.Frontiers in immunology · 2021Article
- Intratubular, Intracellular, and Mitochondrial Angiotensin II/ATFrontiers in physiology · 2021Review
- Article
- Therapeutic Targeting of Endosomal G-Protein-Coupled Receptors.Trends in pharmacological sciences · 2018Review
- Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief.Science translational medicine · 2017Article
- Orthosteric, Allosteric and Biased Signalling at the Relaxin-3 Receptor RXFP3.Neurochemical research · 2016Article
- G Protein-Coupled Receptor Trafficking and Signalling in the Enteric Nervous System: The Past, Present and Future.Advances in experimental medicine and biology · 2016Review
- Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides.Pharmacological reviews · 2015Review
- Endothelin-converting enzyme 2 differentially regulates opioid receptor activity.British journal of pharmacology · 2015Article
- Endothelin-converting enzyme 1 and β-arrestins exert spatiotemporal control of substance P-induced inflammatory signals.The Journal of biological chemistry · 2014Article
- Opioid receptor function is regulated by post-endocytic peptide processing.The Journal of biological chemistry · 2014Article
- Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.The Journal of clinical investigation · 2014Article
- Signalling profiles of H3 relaxin, H2 relaxin and R3(BΔ23-27)R/I5 acting at the relaxin family peptide receptor 3 (RXFP3).British journal of pharmacology · 2014Article
- Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.Physiological reviews · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Neuropeptide signaling at the cell surface is regulated by metalloendopeptidases, which degrade peptides in the extracellular fluid, and beta-arrestins, which interact with G protein-coupled receptors (GPCRs) to mediate desensitization. beta-Arrestins also recruit GPCRs and mitogen-activated protein kinases to endosomes to allow internalized receptors to continue signaling, but the mechanisms regulating endosomal signaling are unknown. We report that endothelin-converting enzyme-1 (ECE-1) degrades substance P (SP) in early endosomes of epithelial cells and neurons to destabilize the endosomal mitogen-activated protein kinase signalosome and terminate signaling. ECE-1 inhibition caused endosomal retention of the SP neurokinin 1 receptor, beta-arrestins, and Src, resulting in markedly sustained ERK2 activation in the cytosol and nucleus, whereas ECE-1 overexpression attenuated ERK2 activation. ECE-1 inhibition also enhanced SP-induced expression and phosphorylation of the nuclear death receptor Nur77, resulting in cell death. Thus, endosomal ECE-1 attenuates ERK2-mediated SP signaling in the nucleus to prevent cell death. We propose that agonist availability in endosomes, here regulated by ECE-1, controls beta-arrestin-dependent signaling of endocytosed GPCRs.
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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.