PKD1, PKD2, and their substrate Kidins220 regulate neurotensin secretion in the BON human endocrine cell line

Jing Li, L. Andy Chen, Courtney Townsend, B. Mark Evers

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Neurotensin (NT) is a gut peptide that plays an important role in gastrointestinal secretion, motility, and growth as well as the proliferation of NT receptor-positive cancers. Protein kinase D (PKD) family members (PKD1, 2, and 3) have been identified as important regulators of secretory transport at the trans-Golgi network. Previously, we showed that PKD1 contributes to stimulated NT secretion; however, the mechanisms are not entirely clear. Here, we show that Kidins220, which is a substrate of PKD proteins in neuroendocrine cells, is localized in the ends of the processes of BON cells, similar to the expression pattern of NT vesicles, and translocates to the membrane and large vesicle-like structures formed in response to phorbol 12-myristate 13-acetate treatment. The short hairpin RNA targeting Kidins220 inhibits NT secretion in parental BON cells or BON cells stably expressing the gastrin-releasing peptide receptor treated with either phorbol 12-myristate 13-acetate or bombesin, respectively. Furthermore, we demonstrate that endogenous PKD1, PKD2, and Kidins220 co-exist with NT-containing vesicles. Overexpression of the kinase-dead PKD1 abrogates Kidins220 expression and NT vesicle formation. Our data establish a physiological link between the PKD/Kidins220 pathway and NT-containing vesicles and suggest the role of this pathway in the regulation of hormone secretion. Because NT is an important gut hormone that affects secretion, inflammation, and both normal and tumor cell growth, our findings identify a novel signaling pathway that may be amenable to drug targeting for clinical applications.

Original languageEnglish (US)
Pages (from-to)2614-2621
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number5
DOIs
StatePublished - Feb 1 2008

Fingerprint

Neurotensin
Endocrine Cells
Cells
Cell Line
Substrates
Acetates
Neurotensin Receptors
Bombesin Receptors
Hormones
trans-Golgi Network
Bombesin
Neuroendocrine Cells
Gastrointestinal Motility
Cell growth
Drug Delivery Systems
Growth
Small Interfering RNA
Tumors
Neoplasms
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

PKD1, PKD2, and their substrate Kidins220 regulate neurotensin secretion in the BON human endocrine cell line. / Li, Jing; Andy Chen, L.; Townsend, Courtney; Evers, B. Mark.

In: Journal of Biological Chemistry, Vol. 283, No. 5, 01.02.2008, p. 2614-2621.

Research output: Contribution to journalArticle

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