PKD3 is the predominant protein kinase D isoform in mouse exocrine pancreas and promotes hormone-induced amylase secretion

L. Andy Chen, Jing Li, Scott R. Silva, Lindsey N. Jackson, Yuning Zhou, Hiroaki Watanabe, Kirk L. Ives, Mark R. Hellmich, B. Mark Evers

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The protein kinase D (PKD) family of serine/threonine kinases, which can be activated by gastrointestinal hormones, consists of three distinct isoforms that modulate a variety of cellular processes including intracellular protein transport as well as constitutive and regulated secretion. Although isoform-specific functions have been identified in a variety of cell lines, the expression and function of PKD isoforms in normal, differentiated secretory tissues is unknown. Here, we demonstrate that PKD isoforms are differentially expressed in the exocrine and endocrine cells of the pancreas. Specifically, PKD3 is the predominant isoform expressed in exocrine cells of the mouse and human pancreas, whereas PKD1 and PKD2 are more abundantly expressed in the pancreatic islets. Within isolated mouse pancreatic acinar cells, PKD3 undergoes rapid membrane translocation, trans-activating phosphorylation, and kinase activation after gastrointestinalhormoneor cholinergic stimulation. PKD phosphorylation in pancreatic acinar cells occurs via a Ca2+- independent, diacylglycerol- and protein kinase C-dependent mechanism. PKD phosphorylation can also be induced by physiologic concentrations of secretagogues and by in vivo stimulation of the pancreas. Furthermore, activation of PKD3 potentiates MEK/ERK/RSK (RSK, ribosomal S6 kinase) signaling and significantly enhances cholecystokinin-mediated pancreatic amylase secretion. These findings reveal a novel distinction between the exocrine and endocrine cells of the pancreas and further identify PKD3 as a signaling molecule that promotes hormone-stimulated amylase secretion.

Original languageEnglish (US)
Pages (from-to)2459-2471
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number4
DOIs
StatePublished - Jan 23 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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