Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells.
Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells.
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胆囊收缩素激活啮齿动物胰腺腺泡细胞中的多种细胞内信号转导机制。
DOI：
10.1034/j.1600-0773.2002.910606.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
A. Dąbrowski
中科院分区：
文献类型：
--
作者：
John A. Williams;M. Dolors Sans;M. Tashiro;C. Schäfer;M. Julia Bragado;A. Dąbrowski
胆囊收缩素（CCK）通过其G蛋白偶联受体激活多种细胞内信号传导机制，从而调节胰腺腺泡细胞复杂的细胞功能。研究最多的机制是通过Gq家族的异源三聚体G蛋白偶联以激活磷脂酶C，导致三磷酸肌醇增加和细胞内Ca 2+释放。该途径沿着蛋白激酶C的活化，响应于二酰基甘油的增加，通过胞吐作用刺激消化酶的分泌。CCK还激活腺泡中与其他过程更相关的信号通路。导致ERK、JNK和p38 MAPK的三个丝裂原活化蛋白激酶级联都被CCK激活。CCK通过PKC激活Raf激活ERK级联，Raf又激活MEK和ERK。JNK通过需要较高浓度CCK的独特机制激活。ERK和JNK都被认为调节基因表达。CCK活化p38 MAPK也通过磷酸化小的热休克蛋白HSP 27在调节肌动蛋白细胞骨架中起作用。PI 3 K-PKB-mTOR途径被CCK激活，在翻译水平调节蛋白质合成方面发挥重要作用。这包括导致核糖体蛋白S6磷酸化的p70 S6 K的活化和导致mRNA帽结合复合物形成的起始因子4 E的结合蛋白的磷酸化。由CCK受体激活的其他信号传导途径包括NF-κ B和多种酪氨酸激酶。需要进一步的工作来了解CCK受体如何激活大多数上述途径，并更好地了解这些不同的信号通路调节的生物学事件。
Cholecystokinin (CCK) acting through its G protein-coupled receptor is now known to activate a variety of intracellular signaling mechanisms and thereby regulate a complex array of cellular functions in pancreatic acinar cells. The best studied mechanism is the coupling through heterotrimeric G proteins of the Gq family to activate a phospholipase C leading to an increase in inositol trisphosphate and release of intracellular Ca2+. This pathway along with protein kinase C activation in response to the increase in diacylglycerol stimulates the secretion of digestive enzymes by the process of exocytosis. CCK also activates signaling pathways in acini more related to other processes. The three mitogen activated protein kinase cascades leading to ERKs, JNKs and p38 MAPK are all activated by CCK. CCK activates the ERK cascade by PKC activation of Raf which in turn activates MEK and ERKs. JNKs are activated by a distinct mechanism which requires higher concentrations of CCK. Both ERKs and JNKs are presumed to regulate gene expression. CCK activation of p38 MAPK also plays a role in regulating the actin cytoskeleton through phosphorylation of the small heat shock protein HSP27. The PI3K-PKB-mTOR pathway is activated by CCK and plays a major role in regulating protein synthesis at the translational level. This includes both activation of p70 S6K leading to phosphorylation of ribosomal protein S6 and the phosphorylation of the binding protein for initiation factor 4E leading to formation of the mRNA cap binding complex. Other signaling pathways activated by CCK receptors include NF-kappaB and a variety of tyrosine kinases. Further work is needed to understand how CCK receptors activate most of the above pathways and to better understand the biological events regulated by these diverse signaling pathways.
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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
发表时间：
1997
期刊：
The American journal of physiology.
影响因子：
--
作者：
Bragado,MJ;Dabrowski,A;Groblewski,GE;Williams,JA
通讯作者：
Williams,JA
胆囊收缩素在体内和体外均可刺激大鼠胰腺中的热休克蛋白 27 磷酸化。
影响因子：
29.4
作者：
Groblewski,GE;Grady,T;Mehta,N;Lambert,H;Logsdon,CD;Landry,J;Williams,JA
通讯作者：
Williams,JA
影响因子：
4
作者：
D. Cantrell
通讯作者：
D. Cantrell
DOI：
10.1152/ajpcell.1999.277.6.c1032
发表时间：
1999-12
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
C. Schäfer;P. Clapp;M. Welsh;R. Benndorf;John A. Williams
通讯作者：
C. Schäfer;P. Clapp;M. Welsh;R. Benndorf;John A. Williams
DOI：
10.1152/ajpcell.1997.273.1.c101
发表时间：
1997-07-01
影响因子：
5.5
作者：
Bragado, MJ;Groblewski, GE;Williams, JA
通讯作者：
Williams, JA