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

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

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere0211134
JournalPloS one
Volume14
Issue number3
DOIs
StatePublished - Mar 2019

ASJC Scopus subject areas

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

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