Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling.
Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal-regulated kinase 1 and 2...
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| Format: | Article |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0211134 |
| _version_ | 1818348519857061888 |
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| author | Stephanie Rock Xian Li Jun Song Courtney M Townsend Heidi L Weiss Piotr Rychahou Tianyan Gao Jing Li B Mark Evers |
| author_facet | Stephanie Rock Xian Li Jun Song Courtney M Townsend Heidi L Weiss Piotr Rychahou Tianyan Gao Jing Li B Mark Evers |
| author_sort | Stephanie Rock |
| collection | DOAJ |
| description | Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal-regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal-regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal-regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling in human endocrine cells. Conversely, we show that overexpression of kinase suppressor of Ras 1 enhances neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling. We also show that inhibition of extracellular signal-regulated kinase 2 and exocyst complex component 70, a substrate of extracellular signal-regulated kinase 2 and mediator of secretory vesicle exocytosis, potently inhibits basal and docosahexaenoic acid-stimulated neurotensin secretion, whereas overexpression of exocyst complex component 70 enhances basal and docosahexaenoic acid-stimulated neurotensin secretion. Together, our findings demonstrate a role for kinase suppressor of Ras 1 as a positive regulator of neurotensin secretion from human endocrine cells and indicate that this effect is mediated by the extracellular signal-regulated kinase 1 and 2 signaling pathway. Moreover, we reveal a novel role for exocyst complex component 70 in regulation of neurotensin vesicle exocytosis through its interaction with the extracellular signal-regulated kinase 1 and 2 signaling pathway. |
| first_indexed | 2024-12-13T17:51:21Z |
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| id | doaj.art-83f425da986342a9a8f7f2d180c41744 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T17:51:21Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-83f425da986342a9a8f7f2d180c417442022-12-21T23:36:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021113410.1371/journal.pone.0211134Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling.Stephanie RockXian LiJun SongCourtney M TownsendHeidi L WeissPiotr RychahouTianyan GaoJing LiB Mark EversNeurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal-regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal-regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal-regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling in human endocrine cells. Conversely, we show that overexpression of kinase suppressor of Ras 1 enhances neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling. We also show that inhibition of extracellular signal-regulated kinase 2 and exocyst complex component 70, a substrate of extracellular signal-regulated kinase 2 and mediator of secretory vesicle exocytosis, potently inhibits basal and docosahexaenoic acid-stimulated neurotensin secretion, whereas overexpression of exocyst complex component 70 enhances basal and docosahexaenoic acid-stimulated neurotensin secretion. Together, our findings demonstrate a role for kinase suppressor of Ras 1 as a positive regulator of neurotensin secretion from human endocrine cells and indicate that this effect is mediated by the extracellular signal-regulated kinase 1 and 2 signaling pathway. Moreover, we reveal a novel role for exocyst complex component 70 in regulation of neurotensin vesicle exocytosis through its interaction with the extracellular signal-regulated kinase 1 and 2 signaling pathway.https://doi.org/10.1371/journal.pone.0211134 |
| spellingShingle | Stephanie Rock Xian Li Jun Song Courtney M Townsend Heidi L Weiss Piotr Rychahou Tianyan Gao Jing Li B Mark Evers Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. PLoS ONE |
| title | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. |
| title_full | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. |
| title_fullStr | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. |
| title_full_unstemmed | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. |
| title_short | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. |
| title_sort | kinase suppressor of ras 1 and exo70 promote fatty acid stimulated neurotensin secretion through erk1 2 signaling |
| url | https://doi.org/10.1371/journal.pone.0211134 |
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