PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades
| Autor: | Marc J. Berna, Veronica Sancho, Michelle Thill, Robert T. Jensen |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pancreatic acini Acinar Cells Rats Sprague-Dawley PKCθ activation Phosphorylation PKC Cells Cultured Protein Kinase C Cholecystokinin Neurotransmitter Agents biology Reverse Transcriptase Polymerase Chain Reaction Pancreas Exocrine Cell biology Isoenzymes Protein Transport src-Family Kinases Pancreatic growth factors Intercellular Signaling Peptides and Proteins raf Kinases Proto-oncogene tyrosine-protein kinase Src Signal Transduction medicine.medical_specialty Cell signaling Blotting Western Real-Time Polymerase Chain Reaction Article Gastrointestinal Hormones LYN Internal medicine medicine Animals Immunoprecipitation Secretion RNA Messenger Protein kinase B Molecular Biology CCK Cell Biology PKCθ activation Signaling Rats Receptor Cholecystokinin A Enzyme Activation Insulin receptor Endocrinology Protein Kinase C-theta biology.protein Proto-Oncogene Proteins c-akt Hormone |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1813(12):2145-2156 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2011.07.007 |
| Popis: | The novel PKCθ isoform is highly expressed in T-cells, brain and skeletal muscle and originally thought to have a restricted distribution. It has been extensively studied in T-cells and shown to be important for apoptosis, T-cell activation and proliferation. Recent studies showed its presence in other tissues and importance in insulin signaling, lung surfactant secretion, intestinal barrier permeability, platelet and mast-cell functions. However, little information is available for PKCθ activation by gastrointestinal (GI) hormones/neurotransmitters and growth factors. In the present study we used rat pancreatic acinar cells to explore their ability to activate PKCθ and the possible interactions with important cellular mediators of their actions. Particular attention was paid to cholecystokinin (CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. PKCθ-protein/mRNA was present in the pancreatic acini, and T538-PKCθ phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK A -receptor activation. CCK stimulated PKCθ translocation from cytosol to membrane. PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125 FAK and IKKα/β, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ's direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKCθ presence in pancreatic acinar cells, its activation by some GI hormones/neurotransmitters and involvement in important cell signaling pathways mediating physiological responses (enzyme secretion, proliferation, apoptosis, cytokine expression, and pathological responses like pancreatitis and cancer growth). |
| Databáze: | OpenAIRE |
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