Temporal Coding of Insulin Action through Multiplexing of the AKT Pathway
Temporal Coding of Insulin Action through Multiplexing of the AKT Pathway
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DOI：
10.1016/j.molcel.2012.04.018
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发表时间：
2012-06-29
期刊：
影响因子：
16
通讯作者：
Kuroda, Shinya
中科院分区：
文献类型：
--
作者：
Kubota, Hiroyuki;Noguchi, Rei;Kuroda, Shinya
细胞信号传导途径的独特特征之一是共同的信号传导途径可以选择性地调节激素的多种细胞功能;然而，通过共同的信号传导途径的这种选择性下游控制知之甚少。在这里，我们表明，胰岛素依赖性AKT途径使用时间模式复用的下游分子的选择性调节。脉冲和持续的胰岛素刺激分别同时编码为瞬时和持续的AKT磷酸化。下游分子，包括核糖体蛋白S6激酶（S6 K）、葡萄糖-6-磷酸酶（G6 Pase）和糖原合成酶激酶-3 β（GSK 3 β），分别选择性地解码瞬时、持续以及瞬时和持续的AKT磷酸化。选择性下游解码由分子的网络结构和动力学介导。我们的研究结果表明，AKT途径可以多重不同的模式的血液胰岛素，如脉冲样的额外和持续样的基础分泌，和下游分子选择性解码分泌模式的胰岛素。
One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient and sustained AKT phosphorylation, respectively. The downstream molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase (G6Pase), and glycogen synthase kinase-3 beta (GSK3 beta) selectively decoded transient, sustained, and both transient and sustained AKT phosphorylation, respectively. Selective downstream decoding is mediated by the molecules' network structures and kinetics. Our results demonstrate that the AKT pathway can multiplex distinct patterns of blood insulin, such as pulse-like additional and sustained-like basal secretions, and the downstream molecules selectively decode secretion patterns of insulin.