Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling

Stephanie Rock; Xian Li; Jun Song; Courtney Townsend; Heidi L. Weiss; Piotr Rychahou; Tianyan Gao; Jing Li; B. Mark Evers

doi:10.1371/journal.pone.0211134

Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling

Stephanie Rock, Xian Li, Jun Song, Courtney Townsend, Heidi L. Weiss, Piotr Rychahou, Tianyan Gao, Jing Li, B. Mark Evers

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Research output: Contribution to journal › Article

Original language	English (US)
Article number	e0211134
Journal	PloS one
Volume	14
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0211134
State	Published - Mar 1 2019

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ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)

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Rock, S., Li, X., Song, J., Townsend, C., Weiss, H. L., Rychahou, P., Gao, T., Li, J., & Mark Evers, B. (2019). Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. PloS one, 14(3), [e0211134]. https://doi.org/10.1371/journal.pone.0211134

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title = "Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling",

abstract = "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.",

author = "Stephanie Rock and Xian Li and Jun Song and Courtney Townsend and Weiss, {Heidi L.} and Piotr Rychahou and Tianyan Gao and Jing Li and {Mark Evers}, B.",

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doi = "10.1371/journal.pone.0211134",

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T1 - Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling

AU - Rock, Stephanie

AU - Li, Xian

AU - Song, Jun

AU - Townsend, Courtney

AU - Weiss, Heidi L.

AU - Rychahou, Piotr

AU - Gao, Tianyan

AU - Li, Jing

AU - Mark Evers, B.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

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10.1371/journal.pone.0211134