PI3K signaling through a biochemical systems lens.
PI3K signaling through a biochemical systems lens.
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DOI：
10.1016/j.jbc.2023.105224
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发表时间：
2023-10
影响因子：
4.8
通讯作者：
Toker, Alex
中科院分区：
文献类型：
--
作者：
Madsen, Ralitsa R.;Toker, Alex
经过30年对PI 3 K信号的广泛研究，现在很明显，底层网络并不等同于简单的ON/OFF开关。与异常PI 3 K信号传导相关的许多疾病的多面性最好地说明了这一点，包括常见的癌症，代谢疾病和罕见的发育障碍。然而，我们仍然远远没有完全理解的基本控制原则，支配众多的表型输出，引起激活这个充分表征的生化信号网络，下游的一组同样不同的外部输入。其核心是关于PI 3 K信号在细胞信息处理和决策中的作用的问题。在这里，我们回顾了生长因子信号的准确编码和解码的决定因素，并讨论了PI 3 K信号中继网络中的突出问题。我们强调定量生物化学的重要性，与单细胞时间分辨信号测量和数学建模的进展密切结合。
Following 3 decades of extensive research into PI3K signaling, it is now evidently clear that the underlying network does not equate to a simple ON/OFF switch. This is best illustrated by the multifaceted nature of the many diseases associated with aberrant PI3K signaling, including common cancers, metabolic disease, and rare developmental disorders. However, we are still far from a complete understanding of the fundamental control principles that govern the numerous phenotypic outputs that are elicited by activation of this well-characterized biochemical signaling network, downstream of an equally diverse set of extrinsic inputs. At its core, this is a question on the role of PI3K signaling in cellular information processing and decision making. Here, we review the determinants of accurate encoding and decoding of growth factor signals and discuss outstanding questions in the PI3K signal relay network. We emphasize the importance of quantitative biochemistry, in close integration with advances in single-cell time-resolved signaling measurements and mathematical modeling.
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