CCK activates p90rsk in rat pancreatic acini through protein kinase C.
CCK activates p90rsk in rat pancreatic acini through protein kinase C.
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CCK 通过蛋白激酶 C 激活大鼠胰腺腺泡中的 p90rsk。
DOI：
10.1152/ajpgi.1997.272.3.g401
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Williams,JA
中科院分区：
文献类型：
--
作者：
Bragado,MJ;Dabrowski,A;Groblewski,GE;Williams,JA
通过蛋白质印迹和抗 p90(rsk) 免疫沉淀证明分离的大鼠胰腺腺泡中存在 90-kDa 核糖体 S6 蛋白激酶 (p90(rsk))。胆囊收缩素 (CCK) 以时间和剂量依赖性方式激活 p90(rsk) 活性并增加其磷酸化。 CCK 的阈值浓度为 10 pM，最大效应为 1 nM。 1 nM CCK 刺激后 1 分钟观察到 p90(rsk) 增加，10 分钟时达到最大值，此时 p90(rsk) 活性增加 5.4 倍。卡巴胆碱和铃蟾肽，但不是血管活性肠肽，也激活 p90(rsk)。 CCK 诱导的 p90(rsk) 激活似乎是由蛋白激酶 C (PKC) 介导的，因为 12-O-十四烷酰佛波醇-13-乙酸酯使 p90(rsk) 活性增加 5.3 倍。 GF-109293X 是一种有效的 PKC 抑制剂，可强烈抑制 CCK 诱发的 p90(rsk) 活性。用离子霉素或1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸处理腺泡没有效果，表明CCK对细胞内Ca2+的动员在p90(rsk)激活中并不重要。尽管抑制程度存在一些定量差异，但特定抑制剂 [雷帕霉素、渥曼青霉素、丝裂原激活蛋白激酶 (MAPK) 激酶抑制剂 PD98059 和 GF-109293X] 对 p90(rsk) 和 p42(mapk) 活性具有平行作用，这与 p90(rsk) 在腺泡中受 MAPK 调节的模型一致。
The presence of the 90-kDa ribosomal S6 protein kinase (p90(rsk)) in isolated rat pancreatic acini was demonstrated by Western blotting and immunoprecipitation with anti-p90(rsk). Cholecystokinin (CCK) activated p90(rsk) activity in a time- and dose-dependent manner and increased its phosphorylation. The threshold concentration of CCK was 10 pM and the maximal effect was seen at 1 nM. An increase in p90(rsk) was observed 1 min after 1 nM CCK stimulation, reaching a maximum at 10 min, when p90(rsk) activity was increased 5.4-fold. Carbachol and bombesin, but not vasoactive intestinal peptide, also activated p90(rsk). CCK-induced activation of p90(rsk) appears to be mediated by protein kinase C (PKC), since 12-O-tetradecanoylphorbol-13-acetate increased p90(rsk) activity 5.3-fold. GF-109293X, a potent inhibitor of PKC, strongly inhibited CCK-evoked p90(rsk) activity. Treatment of acini with ionomycin or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid had no effect, indicating that mobilization of intracellular Ca2+ by CCK is not important in p90(rsk) activation. Although there were some quantitative differences in the extent of inhibition, the specific inhibitors [rapamycin, wortmannin, mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059, and GF-109293X] had parallel effects on p90(rsk) and p42(mapk) activities, consistent with a model in which p90(rsk) can be regulated in acini by MAPK.