Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling
| Autor: | Courtney M. Townsend, Piotr G. Rychahou, Stephanie B. Rock, Jing Li, B. Mark Evers, Heidi L. Weiss, Xian Li, Jun Song, Tianyan Gao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Vesicular Transport Proteins Enteroendocrine cell ERK signaling cascade Biochemistry chemistry.chemical_compound 0302 clinical medicine Endocrinology Cell Signaling Endocrine Signaling Medicine and Health Sciences Small interfering RNAs Post-Translational Modification Phosphorylation Neurotensin Mitogen-Activated Protein Kinase 1 Multidisciplinary Mitogen-Activated Protein Kinase 3 Kinase Chemistry Fatty Acids Signaling cascades Cell biology Nucleic acids 030220 oncology & carcinogenesis Medicine Signal transduction Mitogen-Activated Protein Kinases Cellular Structures and Organelles Protein Binding Signal Transduction Research Article Signal Inhibition MAP Kinase Signaling System Science Enteroendocrine Cells Exocyst Ras Signaling Exocytosis Cell Line 03 medical and health sciences Cell Line Tumor Extracellular Genetics Humans Secretion Vesicles Non-coding RNA Endocrine Physiology Secretory Vesicles Biology and Life Sciences Proteins Cell Biology Gene regulation 030104 developmental biology RNA Gene expression Endocrine Cells Physiological Processes Protein Kinases |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 3, p e0211134 (2019) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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