据悉，蛋白质磷酸化信号网络在细胞如何感知，和响应其环境中起着核心作用。
研究人员设计了人工磷酸化网络，其中由模块化蛋白质结构域部分组装可逆的酶磷酸化循环，并连接在一起，在人类细胞中创建合成磷酸化回路。
他们的设计方案实现了电路功能的模型导向调谐，和多种网络连接的能力。合成的磷酸化回路可以偶联到上游的细胞表面受体，实现细胞外配体的快速时间尺度感应，下游的连接可以调节基因表达。
研究组设计了基于细胞的细胞因子控制器，动态感知和抑制活化的T细胞。他们的工作引入了一种可推广的方法，该方法允许设计信号电路，使热定义的感知和响应功能，能够用于各种生物传感和治疗应用。
附：英文原文
Title: Engineering synthetic phosphorylation signaling networks in human cells
Author: Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang, Andrew J. Walters, Kshitij Rai, Jing Liu, Jason Nguyen, Scott D. Olson, Pankaj Mehta, James J. Collins, Nichole M. Daringer, Caleb J. Bashor
Issue&Volume: 2025-01-03
Abstract: Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression. We engineered cell-based cytokine controllers that dynamically sense and suppress activated T cells. Our work introduces a generalizable approach that allows the design of signaling circuits that enable user-defined sense-and-respond function for diverse biosensing and therapeutic applications.
DOI: adm8485
Source: https://www.science.org/doi/10.1126/science.adm8485