Cholecystokinin stimulates heat shock protein 27 phosphorylation in rat pancreas both in vivo and in vitro.
Cholecystokinin stimulates heat shock protein 27 phosphorylation in rat pancreas both in vivo and in vitro.
复制标题
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。
DOI：
10.1016/s0016-5085(97)70149-5
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发表时间：
1997
期刊：
影响因子：
29.4
通讯作者：
Williams,JA
中科院分区：
文献类型：
--
作者：
Groblewski,GE;Grady,T;Mehta,N;Lambert,H;Logsdon,CD;Landry,J;Williams,JA
哺乳动物热休克蛋白27 （hsp27）被认为在正常生理条件下和细胞应激过程中发挥作用。最近的研究表明，热休克蛋白27在调节肌动蛋白-细胞骨架动力学中的作用。在本研究中，我们在体内和分离的腺泡细胞中研究了分泌激素调节的大鼠外分泌胰腺hsp27的磷酸化。方法采用双向电泳后的western分析法测定分泌剂作用大鼠或腺泡细胞后hsp27的磷酸化水平。免疫沉淀后测定胆囊收缩素刺激的有丝分裂原活化蛋白激酶活化蛋白激酶2的活性。结果shsp27在腺泡中存在三种亚型：一种非磷酸化（pI 6.2），两种磷酸化（pI 5.9和5.7）。给大鼠注入分泌或最大剂量的蓝蛋白可使hsp27发生酸性转移，表明其磷酸化水平增加；已知会引起胰腺炎的较高剂量的效果是前者的两倍。在分离的腺泡中，hsp27磷酸化在10 pmol/L时明显增加，在1 nmol/L胆囊收缩素时最大。在1 nmol/L胆囊收缩素处理下，hsp27特异性激酶MAPKAP激酶2被激活2.4倍。结论体内和体外低、高浓度胆囊收缩素均可刺激shsp27的磷酸化。磷酸化可能通过MAPKAP激酶2细胞内信号通路介导。（胃肠病学1997年4月；112(4):1354-61）
BACKGROUND & AIMSMammalian heat shock protein 27 (hsp27) is believed to function under normal physiological conditions and during cellular stress. Recent studies indicate a role for hsp27 in regulating actin- cytoskeletal dynamics. In the present study, secretagogue-regulated phosphorylation of hsp27 in rat exocrine pancreas was investigated both in vivo and in isolated acinar cells.METHODSWestern analysis after two-dimensional electrophoresis was used to measure the phosphorylation of hsp27 after treatment of rats or acinar cells with secretagogues. Cholecystokinin-stimulated mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 activity was measured after immunoprecipitation of the kinase.RESULTShsp27 exists as three isoforms in acini: one nonphosphorylated (pI 6.2) and two phosphorylated (pIs 5.9 and 5.7) forms. Infusion of rats with a secretory or supermaximal dose of cerulein produced an acidic shift in hsp27, indicating an increase in its phosphorylation; the higher dose, known to cause pancreatitis, had a twofold greater effect. In isolated acini, increases in hsp27 phosphorylation were evident at 10 pmol/L and maximal at 1 nmol/L cholecystokinin. The hsp27-specific kinase MAPKAP kinase 2 was activated 2.4-fold with 1 nmol/L cholecystokinin treatment.CONCLUSIONShsp27 phosphorylation was stimulated by low and high concentrations of cholecystokinin, both in vivo and in vitro. Phosphorylation was potentially mediated via the MAPKAP kinase 2 intracellular signaling pathway. (Gastroenterology 1997 Apr;112(4):1354-61)