PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.
Standard
PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades. / Sancho, Veronica; Berna, Marc; Berna-Thill, Michelle; Jensen, R T.
In: BBA-MOL CELL RES, Vol. 1813, No. 12, 12, 2011, p. 2145-2156.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.
AU - Sancho, Veronica
AU - Berna, Marc
AU - Berna-Thill, Michelle
AU - Jensen, R T
PY - 2011
Y1 - 2011
N2 - The novel PKC? 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 PKC? 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 PKC? 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. PKC?-protein/mRNA was present in the pancreatic acini, and T538-PKC? phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKC? was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. CCK stimulated PKC? translocation from cytosol to membrane. PKC? inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKK?/?, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKC? activation produced an increment in PKC?'s direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKC? 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).
AB - The novel PKC? 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 PKC? 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 PKC? 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. PKC?-protein/mRNA was present in the pancreatic acini, and T538-PKC? phosphorylation/activation was stimulated only by hormones/neurotransmitters activating phospholipase C. PKC? was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. CCK stimulated PKC? translocation from cytosol to membrane. PKC? inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKK?/?, but not basal/stimulated enzyme secretion. Also CCK- and TPA-induced PKC? activation produced an increment in PKC?'s direct association with AKT, RafA, RafC and Lyn. These results show for the first time the PKC? 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).
M3 - SCORING: Journal article
VL - 1813
SP - 2145
EP - 2156
JO - BBA-MOL CELL RES
JF - BBA-MOL CELL RES
SN - 0167-4889
IS - 12
M1 - 12
ER -