Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth.
Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth.
复制标题
DOI：
10.3389/fphys.2023.1147572
复制
发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
前言：肌动蛋白调节蛋白Cofilin在许多细胞中起着关键的信号作用，参与细胞的增殖、发育、运动、迁移、分泌和生长。在胰腺中，它对胰岛胰岛素的分泌、胰腺癌细胞的生长和胰腺炎都很重要。然而，目前还没有关于其在胰腺腺泡细胞中的作用或激活的研究。方法：研究CCK在胰腺腺泡细胞、AR42J细胞和转导CCK1-R的PANC-1细胞中激活cofilin的能力，信号转导途径及其对酶分泌和MAPK激活的影响。结果：CCK(0.3和100nM)、TPA、卡巴胆碱、蛙黄素、促胰液素和VIP均可降低Cofilin的磷酸化活性(即激活Cofilin)，Cofilin、LIM激酶(LIMK)和Slingshot蛋白磷酸酶(SSH1)的磷酸化动力学和抑制研究均表明这些常规的Cofilin激活剂不参与。丝氨酸磷酸酶抑制剂(花盏草素A和冈田酸)则抑制CCK/TPA-cofilin的激活。对CCK激活的各种信号通路的研究表明，PKC/PKD、Src、PAK4、JNK、ROCK介导的cofilin激活，而不是PI3K、p38或MEK的激活。此外，使用siRNA和Cofilin抑制剂，Cofilin的激活对于CCK介导酶的分泌和MAPK的激活是必不可少的。结论：在CCK介导的胰腺腺泡细胞生长/酶分泌过程中，cofilin激活在多种细胞信号通路中起着关键的汇聚作用。
Introduction: The actin regulatory protein, cofilin plays a key signaling role in many cells for numerous cellular responses including in proliferation, development, motility, migration, secretion and growth. In the pancreas it is important in islet insulin secretion, growth of pancreatic cancer cells and in pancreatitis. However, there are no studies on its role or activation in pancreatic acinar cells. Methods: To address this question, we studied the ability of CCK to activate cofilin in pancreatic acinar cells, AR42J cells and CCK1-R transfected Panc-1 cells, the signaling cascades involved and its effect on enzyme secretion and MAPK activation, a key mediator of pancreatic growth. Results: CCK (0.3 and 100 nM), TPA, carbachol, Bombesin, secretin and VIP decreased phospho-cofilin (i.e., activate cofilin) and both phospho‐kinetic and inhibitor studies of cofilin, LIM kinase (LIMK) and Slingshot Protein Phosphatase (SSH1) demonstrated these conventional activators of cofilin were not involved. Serine phosphatases inhibitors (calyculin A and okadaic acid), however inhibited CCK/TPA-cofilin activation. Studies of various CCK‐activated signaling cascades showed activation of PKC/PKD, Src, PAK4, JNK, ROCK mediated cofilin activation, but not PI3K, p38, or MEK. Furthermore, using both siRNA and cofilin inhibitors, cofilin activation was shown to be essential for CCK-mediated enzyme secretion and MAPK activation. Conclusion: These results support the conclusion that cofilin activation plays a pivotal convergent role for various cell signaling cascades in CCK mediated growth/enzyme secretion in pancreatic acini.
登录
查看更多内容
DOI：
10.1016/j.bbamcr.2011.07.007
发表时间：
2011-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Sancho V;Berna MJ;Thill M;Jensen RT
通讯作者：
Jensen RT
影响因子：
3.7
作者：
Döppler H;Bastea LI;Borges S;Spratley SJ;Pearce SE;Storz P
通讯作者：
Storz P
影响因子：
21.3
作者：
Eiseler T;Döppler H;Yan IK;Kitatani K;Mizuno K;Storz P
通讯作者：
Storz P
DOI：
10.1006/bbrc.2001.5435
发表时间：
2001-08-24
影响因子：
3.1
作者：
Birkenfeld, J;Kartmann, B;Roth, D
通讯作者：
Roth, D
影响因子：
64.8
作者：
Cho, Uhn Soo;Xu, Wenqing
通讯作者：
Xu, Wenqing