ArticleBiochemistry2011
Thrombospondin-1 and angiotensin II inhibit soluble guanylyl cyclase through an increase in intracellular calcium concentration.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- T Cell Activation Induces Synthesis of CD47 Proteoglycan Isoforms and Their Release in Extracellular Vesicles.International journal of molecular sciences · 2025Article
- Per-ARNT-Sim Domains in Nitric Oxide Signaling by Soluble Guanylyl Cyclase.Journal of molecular biology · 2024Review
- Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase.Cells · 2023Review
- Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling.Biomedicines · 2022Article
- CD47 differentially regulates white and brown fat function.Biology open · 2020Article
- Thrombospondin-1 in maladaptive aging responses: a concept whose time has come.American journal of physiology. Cell physiology · 2020Review
- Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- The role of CD47 in pathogenesis and treatment of renal ischemia reperfusion injury.Pediatric nephrology (Berlin, Germany) · 2019Review
- Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase.The Journal of biological chemistry · 2018Article
- Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.Antioxidants & redox signaling · 2017Article
- A Novel β-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis.Scientific reports · 2017Article
- Vascular transcriptome profiling identifies Sphingosine kinase 1 as a modulator of angiotensin II-induced vascular dysfunction.Scientific reports · 2017Article
- Nitric oxide: what's new to NO?American journal of physiology. Cell physiology · 2017Review
- Structure and Activation of Soluble Guanylyl Cyclase, the Nitric Oxide Sensor.Antioxidants & redox signaling · 2017Review
- CD47 deficiency protects mice from diet-induced obesity and improves whole body glucose tolerance and insulin sensitivity.Scientific reports · 2015Article
- Original insights on thrombospondin-1-related antireceptor strategies in cancer.Frontiers in pharmacology · 2015Review
- CD47 signaling pathways controlling cellular differentiation and responses to stress.Critical reviews in biochemistry and molecular biology · 2015Review
- CD47-dependent regulation of H₂S biosynthesis and signaling in T cells.Methods in enzymology · 2015Article
- CD47 in the tumor microenvironment limits cooperation between antitumor T-cell immunity and radiotherapy.Cancer research · 2014Article
- Thrombospondin-1 and CD47 regulation of cardiac, pulmonary and vascular responses in health and disease.Matrix biology : journal of the International Society for Matrix Biology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nitric oxide (NO) regulates cardiovascular hemostasis by binding to soluble guanylyl cyclase (sGC), leading to cGMP production, reduced cytosolic calcium concentration ([Ca(2+)](i)), and vasorelaxation. Thrombospondin-1 (TSP-1), a secreted matricellular protein, was recently discovered to inhibit NO signaling and sGC activity. Inhibition of sGC requires binding to cell-surface receptor CD47. Here, we show that a TSP-1 C-terminal fragment (E3CaG1) readily inhibits sGC in Jurkat T cells and that inhibition requires an increase in [Ca(2+)](i). Using flow cytometry, we show that E3CaG1 binds directly to CD47 on the surface of Jurkat T cells. Using digital imaging microscopy on live cells, we further show that E3CaG1 binding results in a substantial increase in [Ca(2+)](i), up to 300 nM. Addition of angiotensin II, a potent vasoconstrictor known to increase [Ca(2+)](i), also strongly inhibits sGC activity. sGC isolated from calcium-treated cells or from cell-free lysates supplemented with Ca(2+) remains inhibited, while addition of kinase inhibitor staurosporine prevents inhibition, indicating inhibition is likely due to phosphorylation. Inhibition is through an increase in K(m) for GTP, which rises to 834 μM for the NO-stimulated protein, a 13-fold increase over the uninhibited protein. Compounds YC-1 and BAY 41-2272, allosteric stimulators of sGC that are of interest for treating hypertension, overcome E3CaG1-mediated inhibition of NO-ligated sGC. Taken together, these data suggest that sGC not only lowers [Ca(2+)](i) in response to NO, inducing vasodilation, but also is inhibited by high [Ca(2+)](i), providing a fine balance between signals for vasodilation and vasoconstriction.
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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.