Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in ames dwarf mice
Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in ames dwarf mice
复制标题
DOI：
10.1093/gerona/60.3.293
复制
发表时间：
2005-03-01
影响因子：
5.1
通讯作者：
Bartke, A
中科院分区：
文献类型：
--
作者：
Sharp, ZD;Bartke, A
生长激素(GH)如何刺激蛋白质合成尚不清楚。磷脂酰肌醇3-激酶/Akt/哺乳动物雷帕霉素靶标(PI3K/Akt/mTOR)信号通路平衡合成代谢和分解代谢活性，以响应营养和生长因子信号。作为生长激素信号的测试，两种下游翻译调节蛋白的免疫测定在自由喂养的2个月大的正常和Ames(Prop1df)侏儒小鼠中进行了比较。侏儒症患者肝脏中S6激酶1的p70和p85亚型以及腓肠肌中的p70亚型的磷酸化水平显著降低。信使RNA(MRNA)帽结合显示矮小肝脏的翻译抑制因子4E-BP1/真核细胞起始因子4E(EIF4E)(共沉淀物)水平显著升高，但肌肉中没有。与这些结合数据一致的是，4E-BP1在矮小肝脏中的磷酸化水平显著降低。这些数据表明，在延长寿命的模型中，生长激素信号和翻译控制之间存在联系。
How growth hormone (GH) stimulates protein synthesis is unknown. Phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways balance anabolic and catabolic activities in response to nutrients and growth factor signaling. As a test of GH signaling, immunoassays of two downstream translation regulatory proteins were compared in ad libitum-fed 2-month-old normal and Ames (Prop1df) dwarf mice. Phosphorylation of the p70 and p85 isoforms of S6 kinase 1 in liver and the p70 isoform in gastrocnemius muscle were significantly decreased in dwarfs. Messenger RNA (mRNA) Cap-binding demonstrated significantly higher levels of translation repressor 4E-BP1/eukaryotic initiation factor 4E (eIF4E) (coprecipitates) from dwarf livers, but not muscle. Consistent with these binding data, significantly less phosphorylation of 4E-BP1 was documented in dwarf liver. These data suggest a link between GH signaling and translation control in a model of extended longevity.