Role of the PI3K/PKB signaling pathway in cAMP-mediated translocation of rat liver Ntcp.
Role of the PI3K/PKB signaling pathway in cAMP-mediated translocation of rat liver Ntcp.
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PI3K/PKB 信号通路在 cAMP 介导的大鼠肝脏 Ntcp 易位中的作用。
DOI：
10.1152/ajpgi.1999.277.6.g1165
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Anwer,MS
中科院分区：
文献类型：
--
作者：
Webster,CR;Anwer,MS
CAMP通过将Na+-TC共转运肽(Ntcp)转运到质膜来刺激Na+-TC共转运。本研究旨在探讨磷脂酰肌醇-3-激酶(PI3K)信号通路是否参与cAMP介导的Ntcp转位。肝细胞经PI3K抑制剂Wortmannin或LY-294002处理后，cAMP刺激TC摄取的能力明显下降。Wortmannin抑制cAMP介导的Ntcp向质膜的转位。CAMP在5min内使蛋白激酶B(PKB)活性增加一倍，Wortmannin可抑制该作用。Wortmannin不影响基础丝裂原活化蛋白激酶(MAPK)活性，也不影响cAMP介导的MAPK活性抑制。CAMP还能刺激p70S6K的活性。然而，p70S6K的抑制剂雷帕霉素不能抑制cAMP介导的TC摄取的刺激作用，表明cAMP的作用不是通过p70S6K介导的。细胞松弛素D是肌动蛋白细丝形成的抑制剂，它抑制cAMP刺激TC摄取和Ntcp转位的能力。综上所述，这些结果提示cAMP对TC摄取和Ntcp转位的刺激可能是通过PI3K/PKB信号通路介导的，需要完整的肌动蛋白细丝。
cAMP stimulates Na+-taurocholate (TC) cotransport by translocating the Na+-TC-cotransporting peptide (Ntcp) to the plasma membrane. The present study was undertaken to determine whether the phosphatidylinositol-3-kinase (PI3K)-signaling pathway is involved in cAMP-mediated translocation of Ntcp. The ability of cAMP to stimulate TC uptake declined significantly when hepatocytes were pretreated with PI3K inhibitors wortmannin or LY-294002. Wortmannin inhibited cAMP-mediated translocation of Ntcp to the plasma membrane. cAMP stimulated protein kinase B (PKB) activity by twofold within 5 min, an effect inhibited by wortmannin. Neither basal mitogen-activated protein kinase (MAPK) activity nor cAMP-mediated inhibition of MAPK activity was affected by wortmannin. cAMP also stimulated p70S6Kactivity. However, rapamycin, an inhibitor of p70S6K, failed to inhibit cAMP-mediated stimulation of TC uptake, indicating that the effect of cAMP is not mediated via p70S6K. Cytochalasin D, an inhibitor of actin filament formation, inhibited the ability of cAMP to stimulate TC uptake and Ntcp translocation. Together, these results suggest that the stimulation of TC uptake and Ntcp translocation by cAMP may be mediated via the PI3K/PKB signaling pathway and requires intact actin filaments.