PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.
PKCθ activation in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors is needed for stimulation of numerous important cellular signaling cascades.
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DOI：
10.1016/j.bbamcr.2011.07.007
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Jensen RT
中科院分区：
文献类型：
--
作者：
Sancho V;Berna MJ;Thill M;Jensen RT
新的PKCθ亚型在T细胞、脑和骨骼肌中高度表达，最初认为其分布有限。它已在T细胞中被广泛研究，并显示对细胞凋亡、T细胞活化和增殖很重要。最近的研究表明，它存在于其他组织和胰岛素信号，肺表面活性物质分泌，肠屏障通透性，血小板和肥大细胞功能的重要性。然而，关于胃肠道（GI）激素/神经递质和生长因子激活PKCθ的信息很少。在本研究中，我们使用大鼠胰腺腺泡细胞，以探讨其激活PKCθ的能力和可能的相互作用与重要的细胞介质的行动。特别注意胆囊收缩素（CCK），胰腺功能的生理调节剂和重要的病理过程中影响腺泡功能，如胰腺炎。胰腺腺泡中存在PKCθ-蛋白/mRNA，T538-PKCθ磷酸化/激活仅由激活磷脂酶C的激素/神经递质刺激。CCK对PKCθ的激活呈时间和剂量依赖性，其中30%由高亲和力CCK A受体介导。CCK刺激PKCθ从胞浆向胞膜转位。PKCθ抑制（通过假策略抑制剂或显性阴性）抑制PKD、Src、RafC、PYK 2、p125 FAK和IKKα/β的CCK和TPA刺激，但不抑制基础/刺激的酶分泌。CCK和TPA诱导的PKCθ激活也使PKCθ与AKT、RafA、RafC和林恩的直接联系增加。这些结果首次表明PKCθ存在于胰腺腺泡细胞中，其被一些GI激素/神经递质激活，并参与介导生理反应（酶分泌、增殖、凋亡、细胞因子表达和病理反应如胰腺炎和癌症生长）的重要细胞信号传导途径。
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 were 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 CCKA-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, p125FAK 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 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).
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DOI：
10.1111/j.1440-1746.2007.05282.x
发表时间：
2008-03-01
影响因子：
4.1
作者：
Gorelick, Fred;Pandol, Stephen;Thrower, Edwin
通讯作者：
Thrower, Edwin
影响因子：
--
作者：
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通讯作者：
JENSEN, RT
DOI：
10.1016/0167-4889(95)00120-0
发表时间：
1995-11-30
影响因子：
5.1
作者：
BASTANI, B;YANG, LY;GARDNER, JD
通讯作者：
GARDNER, JD
影响因子：
5.3
作者：
Adhikari S;Bhatia M
通讯作者：
Bhatia M
DOI：
10.1046/j.1432-1033.2003.03869.x
发表时间：
2003-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Andreolotti, AG;Bragado, MJ;Garcia-Marin, LJ
通讯作者：
Garcia-Marin, LJ