Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address the question of how the ERK pathway exerts distinct and context-specific effects on multiple processes. We discuss how the dynamics of ERK activity induce selective changes in gene expression programs, with insights from both experiments and computational models. With a focus on single-cell biosensor-based studies, we summarize four major functional modes for ERK signaling in tissues: adjusting the size of cell populations, gradient-based patterning, wave propagation of morphological changes, and diversification of cellular gene expression states. These modes of operation are disrupted in cancer and other related diseases and represent potential targets for therapeutic intervention. By understanding the dynamic mechanisms involved in ERK signaling, there is potential for pharmacological strategies that not only simply inhibit ERK, but also restore functional activity patterns and improve disease outcomes.

中文翻译：

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ERK 动态指南，第 2 部分：下游解码

细胞外信号调节激酶 (ERK) 通路的信号传导控制许多细胞过程，包括细胞分裂、死亡和分化。在由两部分组成的综述的第二部分中，我们解决了 ERK 通路如何对多个过程发挥独特且特定于环境的影响的问题。我们通过实验和计算模型的见解，讨论了 ERK 活性的动态如何诱导基因表达程序的选择性变化。重点关注基于单细胞生物传感器的研究，我们总结了组织中 ERK 信号传导的四种主要功能模式：调整细胞群的大小、基于梯度的模式、形态变化的波传播以及细胞基因表达状态的多样化。这些操作模式在癌症和其他相关疾病中被破坏，并代表了治疗干预的潜在目标。通过了解 ERK 信号转导所涉及的动态机制，我们有可能发现药理学策略不仅可以简单地抑制 ERK，还可以恢复功能活动模式并改善疾病结果。