A guide to ERK dynamics, part 1: mechanisms and models.
A guide to ERK dynamics, part 1: mechanisms and models.
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ERK动力学指南，第1部分：机制和模型。
DOI：
10.1042/bcj20230276
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发表时间：
2023-12-13
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞外信号调节激酶（ERK）长期以来一直被研究为基本细胞过程和疾病的关键驱动因素。一个持续存在的问题是，这一单一途径如何能够指导多种细胞行为，包括生长，增殖和死亡。现代生物传感器研究表明，ERK活性的时间模式是高度可变和异质性的，关键是，这些动态差异调节细胞命运。这两部分的审查讨论了目前的理解ERK通路的动态活动，它如何调节细胞的决定，以及这些细胞的命运如何导致组织调节和病理。在第1部分中，我们介绍了首次揭示ERK动态性质的光遗传学和活细胞成像技术，以及生物传感器数据分析中的当前挑战。我们还讨论了ERK动力学机制的数学模型的进展，包括受体水平的调节，负反馈，协同性和旁分泌信号。虽然障碍仍然存在，但很明显，更高的时间和空间分辨率提供了对通路电路的机械见解。令人兴奋的新算法和先进的计算工具使单细胞ERK激活的定量测量成为可能，从而为更好的通路行为模型提供信息。然而，事实上，目前的模型仍然不能完全概括ERK反应的多样性，需要更深入地了解网络结构和信号转导一般。
Extracellular signal-regulated kinase (ERK) has long been studied as a key driver of both essential cellular processes and disease. A persistent question has been how this single pathway is able to direct multiple cell behaviors, including growth, proliferation, and death. Modern biosensor studies have revealed that the temporal pattern of ERK activity is highly variable and heterogeneous, and critically, that these dynamic differences modulate cell fate. This two-part review discusses the current understanding of dynamic activity in the ERK pathway, how it regulates cellular decisions, and how these cell fates lead to tissue regulation and pathology. In part 1, we cover the optogenetic and live-cell imaging technologies that first revealed the dynamic nature of ERK, as well as current challenges in biosensor data analysis. We also discuss advances in mathematical models for the mechanisms of ERK dynamics, including receptor-level regulation, negative feedback, cooperativity, and paracrine signaling. While hurdles still remain, it is clear that higher temporal and spatial resolution provide mechanistic insights into pathway circuitry. Exciting new algorithms and advanced computational tools enable quantitative measurements of single-cell ERK activation, which in turn inform better models of pathway behavior. However, the fact that current models still cannot fully recapitulate the diversity of ERK responses calls for a deeper understanding of network structure and signal transduction in general.
具有时间生长因子递送的微流体设备的设计和实现揭示了EGFR/ERK途径的过滤功能。
影响因子：
6
作者：
Krause HB;Bondarowicz H;Karls AL;McClean MN;Kreeger PK
通讯作者：
Kreeger PK
数据驱动的建模可以调解ERK磷酸化，定位和活动状态的动力学。
影响因子：
9.9
作者：
Ahmed, Shoeb;Grant, Kyle G.;Edwards, Laura E.;Rahman, Anisur;Cirit, Murat;Goshe, Michael B.;Haugh, Jason M.
通讯作者：
Haugh, Jason M.