PKD3 is the predominant protein kinase D isoform in mouse exocrine pancreas and promotes hormone-induced amylase secretion.
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 gastrointestinal hormone or cholinergic stimulation. PKD phosphorylation in pancreatic acinar cells occurs viaaCa2+-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.
Chen
L Andy
LA
Department of Surgery and Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-0536, USA.
Li
Jing
J
Silva
Scott R
SR
Jackson
Lindsey N
LN
Zhou
Yuning
Y
Watanabe
Hiroaki
H
Ives
Kirk L
KL
Hellmich
Mark R
MR
Evers
B Mark
BM
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D019742:Chemokines, CC / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D012469:Salivary Glands / Q000201:enzymology; D015398:Signal Transduction
D019742:Chemokines, CC; D006728:Hormones; D007527:Isoenzymes; C089212:protein kinase D; D011493:Protein Kinase C; D000681:Amylases