ArticleThe Journal of biological chemistry2014
Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Liver sinusoidal endothelial cells secret C-X-C motif chemokine ligand 10 to promote the recruitment of invariant NKT cells in acetaminophen-induced liver injury.Science China. Life sciences · 2025Article
- The effects of 5-HT on vascular endothelial dysfunction in patients with panic disorder.Frontiers in cardiovascular medicine · 2025Review
- Hepatic β-arrestins: potential roles in liver health and disease.Molecular biology reports · 2023Review
- Angiocrine Signaling in Sinusoidal Health and Disease.Seminars in liver disease · 2023Review
- Low testosterone state inhibits erectile function by downregulating the expression of GIT1 in rat penile corpus cavernosum.Sexual medicine · 2023Article
- Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.FEBS open bio · 2021Article
- Association ofIranian journal of basic medical sciences · 2021Article
- Disruptions of Circadian Rhythms and Thrombolytic Therapy During Ischemic Stroke Intervention.Frontiers in neuroscience · 2021Review
- Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway.Scientific reports · 2020Article
- β-Arrestin2 is a critical component of the GPCR-eNOS signalosome.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Lung Endothelial Transcytosis.Comprehensive Physiology · 2020Review
- Anti-apoptotic activity of ETScientific reports · 2019Article
- Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study.International journal of molecular sciences · 2018Review
- Deletion of T-type calcium channels CaPflugers Archiv : European journal of physiology · 2018Article
- Biology of portal hypertension.Hepatology international · 2018Review
- Nitric oxide: what's new to NO?American journal of physiology. Cell physiology · 2017Review
- The Molecular Basis of Portal Hypertension.Transactions of the American Clinical and Climatological Association · 2017Review
- The eNOS signalosome and its link to endothelial dysfunction.Pflugers Archiv : European journal of physiology · 2016Review
- Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.Oncotarget · 2016Article
- Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.PloS one · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production.
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