ArticleThe Journal of biological chemistry2012
Receptor tyrosine kinase Ephb6 regulates vascular smooth muscle contractility and modulates blood pressure in concert with sex hormones.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.Scientific reports · 2018Trial
- Adaptation of Diqing Tibetan pigs to hypoxic and cold environments through extramedullary hematopoiesis and uncoupled thermogenesis in the liver.BMC biology · 2025Article
- Development of a novel anti-erythropoietin-producing hepatocellular receptor B6 monoclonal antibody EbBiochemistry and biophysics reports · 2025Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- GWAS-based polygenic risk scoring for predicting cerebral artery dissection in the Chinese population.BMC neurology · 2024Article
- Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size.Molecular biology reports · 2024Article
- Identification of Sex-Specific Genetic Polymorphisms Associated with Asthma in Middle-Aged and Older Canadian Adults: An Analysis of CLSA Data.Journal of asthma and allergy · 2023Article
- Cooccurring Type 1 Diabetes Mellitus and Autoimmune Thyroiditis in a Girl with Craniofrontonasal Syndrome: ArePharmaceuticals (Basel, Switzerland) · 2022Article
- Glutamate receptor-interacting protein 1 in D1- and D2-dopamine receptor-expressing medium spiny neurons differentially regulates cocaine acquisition, reinstatement, and associated spine plasticity.Frontiers in cellular neuroscience · 2022Article
- Free Fatty Acid Species Differentially Modulate the Inflammatory Gene Response in Primary Human Skeletal Myoblasts.Biology · 2021Article
- The EphB6 Receptor: Kinase-Dead but Very Much Alive.International journal of molecular sciences · 2021Review
- Activation of EphrinB2 Signaling Promotes Adaptive Venous Remodeling in Murine Arteriovenous Fistulae.The Journal of surgical research · 2021Article
- Structure of the EphB6 receptor ectodomain.PloS one · 2021Article
- The receptor tyrosine kinase EPHB6 regulates catecholamine exocytosis in adrenal gland chromaffin cells.The Journal of biological chemistry · 2020Article
- A Variant in the Nicotinic Acetylcholine Receptor Alpha 3 Subunit Gene Is Associated With Hypertension Risks in Hypogonadic Patients.Frontiers in genetics · 2020Article
- Review
- EPHB6 controls catecholamine biosynthesis by up-regulating tyrosine hydroxylase transcription in adrenal gland chromaffin cells.The Journal of biological chemistry · 2019Article
- EPHB6 and testosterone in concert regulate epinephrine release by adrenal gland chromaffin cells.Scientific reports · 2018Article
- Guidance Molecules in Vascular Smooth Muscle.Frontiers in physiology · 2018Review
- EPHA6 rs4857055 C > T polymorphism associates with hypertension through triglyceride and LDL particle size in the Korean population.Lipids in health and disease · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Eph kinases constitute the largest receptor tyrosine kinase family, and their ligands, ephrins (Efns), are also cell surface molecules. Our study is the first to assess the role of Ephb6 in blood pressure (BP) regulation. We observed that EphB6 and all three of its Efnb ligands were expressed on vascular smooth muscle cells (VSMC) in mice. We discovered that small arteries from castrated Ephb6 gene KO males showed increased contractility, RhoA activation, and constitutive myosin light chain phosphorylation ex vivo compared with their WT counterparts. Consistent with this finding, castrated Ephb6 KO mice presented heightened BP compared with castrated WT controls. In vitro experiments in VSMC revealed that cross-linking Efnbs but not Ephb6 resulted in reduced VSMC contractions, suggesting that reverse signaling through Efnbs was responsible for the observed BP phenotype. The reverse signaling was mediated by an adaptor protein Grip1. Additional experiments demonstrated decreased 24-h urine catecholamines in male Ephb6 KO mice, probably as a compensatory feedback mechanism to keep their BP in the normal range. After castration, however, such compensation was abolished in Ephb6 KO mice and was likely the reason why BP increased overtly in these animals. It suggests that Ephb6 has a target in the nervous/endocrine system in addition to VSMC, regulating a testosterone-dependent catecholamine compensatory mechanism. Our study discloses that Ephs and Efns, in concert with testosterone, play a critical role in regulating small artery contractility and BP.
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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.