ß‐Arrestin 2 is required for B1 receptor‐dependent post‐translational activation of inducible nitric oxide synthase
| العنوان: | ß‐Arrestin 2 is required for B1 receptor‐dependent post‐translational activation of inducible nitric oxide synthase |
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| المؤلفون: | Yongkang Zhang, Randal A. Skidgel, Viktor Brovkovych, Frank K. Kuhr |
| المصدر: | The FASEB Journal. 24:2475-2483 |
| بيانات النشر: | Wiley, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | MAPK/ERK pathway, medicine.medical_specialty, Endothelium, Arrestins, Nitric Oxide Synthase Type II, Receptor, Bradykinin B1, Biochemistry, Cell Line, Research Communications, Enzyme activator, Internal medicine, Genetics, medicine, Humans, Extracellular Signal-Regulated MAP Kinases, Receptor, Lung, Molecular Biology, beta-Arrestins, Inflammation, Gene knockdown, biology, Beta-Arrestins, Chemistry, Transfection, beta-Arrestin 2, Cell biology, Enzyme Activation, Nitric oxide synthase, beta-Arrestin 1, medicine.anatomical_structure, Endocrinology, biology.protein, Endothelium, Vascular, Biotechnology |
| الوصف: | A major source of “high-output” NO in inflammation is inducible nitric oxide synthase (iNOS). iNOS is primarily transcriptionally regulated and is thought to function as an uncontrolled generator of high NO. We found that iNOS in cytokine-stimulated human lung microvascular endothelial cells (HLMVECs) is highly regulated post-translationally via activation of the B1 kinin G protein-coupled receptor (B1R). We report here that B1R-mediated iNOS activation was significantly inhibited by knockdown of β-arrestin 2 with siRNA in cytokine-treated HLMVECs or HEK293 cells transfected with iNOS and B1R. In contrast, β-arrestin 1 siRNA had no effect. The prolonged phase of B1R-dependent ERK activation was also inhibited by β-arrestin 2 knockdown. Furthermore, robust ERK activation by the epidermal growth factor receptor (a β-arrestin 2 independent pathway) had no effect on iNOS-derived NO production. β-arrestin 2 and iNOS coimmunoprecipitated, and there was significant fluorescence resonance energy transfer between CFP-iNOS and β-arrestin 2-YFP (but not β-arrestin 1-YFP) that increased 3-fold after B1R stimulation. These data show that β-arrestin 2 mediates B1R-dependent high-output NO by scaffolding iNOS and ERK to allow post-translational activation of iNOS. This could play a critical role in mediating endothelial function in inflammation.—Kuhr, F. K., Zhang, Y., Brovkovych, V., Skidgel, R. A. β-Arrestin 2 is required for B1 receptor-dependent post-translational activation of inducible nitric oxide synthase. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c35af12ce609e1f89a6a46903ac7bf7Test https://doi.org/10.1096/fj.09-148783Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0c35af12ce609e1f89a6a46903ac7bf7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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