دورية أكاديمية
Signal profiling of the β1AR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by β1AR and β2AR
| العنوان: | Signal profiling of the β1AR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by β1AR and β2AR |
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| المؤلفون: | Lukasheva, Viktoriya, Devost, Dominic, Le Gouill, Christian, Namkung, Yoon, Martin, Ryan D., Longpré, Jean-Michel, Amraei, Mohammad, Shinjo, Yuji, Hogue, Mireille, Lagacé, Monique, Breton, Billy, Aoki, Junken, Tanny, Jason C., Laporte, Stéphane A., Pineyro, Graciela, Inoue, Asuka, Bouvier, Michel, Hébert, Terence E. |
| المصدر: | Scientific Reports ; volume 10, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | A comprehensive understanding of signalling downstream of GPCRs requires a broad approach to capture novel signalling modalities in addition to established pathways. Here, using an array of sixteen validated BRET-based biosensors, we analyzed the ability of seven different β-adrenergic ligands to engage five distinct signalling pathways downstream of the β 1 -adrenergic receptor (β 1 AR). In addition to generating signalling signatures and capturing functional selectivity for the different ligands toward these pathways, we also revealed coupling to signalling pathways that have not previously been ascribed to the βAR. These include coupling to G z and G 12 pathways. The signalling cascade linking the β 1 AR to calcium mobilization was also characterized using a combination of BRET-based biosensors and CRISPR-engineered HEK 293 cells lacking the Gαs subunit or with pharmacological or genetically engineered pathway inhibitors. We show that both G s and G 12 are required for the full calcium response. Our work highlights the power of combining signal profiling with genome editing approaches to capture the full complement of GPCR signalling activities in a given cell type and to probe their underlying mechanisms. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-020-65636-3 |
| الإتاحة: | https://doi.org/10.1038/s41598-020-65636-3Test https://www.nature.com/articles/s41598-020-65636-3.pdfTest https://www.nature.com/articles/s41598-020-65636-3Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.4C7237F0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-020-65636-3 |
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