Department of Pharmacology, UT Southwestern Medical Center, 6001 Forest Park Rd., Dallas, TX 75390, USA.
Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, 6001 Forest Park Rd., Dallas, TX 75390, USA.
Biomolecules. 2023 Oct 20;13(10):1555. doi: 10.3390/biom13101555.
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic β-cells. Alterations in the different components of this cascade result in dysregulation of the effector kinases ERK1/2 which communicate with hundreds of substrates. Aberrant activation of the pathway contributes to a range of disorders, including cancer. This review provides an overview of the structure, activation, regulation, and mutational frequency of the different tiers of the cascade; with a particular focus on ERK1/2. We highlight the importance of scaffold proteins that contribute to kinase localization and coordinate interaction dynamics of the kinases with substrates, activators, and inhibitors. Additionally, we explore innovative therapeutic approaches emphasizing promising avenues in this field.
RAS-ERK 通路是一个基本的信号级联反应，对许多生物过程至关重要，包括增殖、细胞周期控制、生长和存活；在所有细胞类型中都很常见。值得注意的是，ERK1/2 在特定的过程中以依赖于上下文的方式被牵连，如在干细胞和胰腺β细胞中。这个级联反应的不同组成部分的改变导致效应激酶 ERK1/2 的失调，ERK1/2 与数百种底物进行通讯。该途径的异常激活导致一系列疾病，包括癌症。这篇综述提供了一个概述，介绍了级联反应的不同层次的结构、激活、调节和突变频率；特别关注 ERK1/2。我们强调了支架蛋白的重要性，这些蛋白有助于激酶的定位，并协调激酶与底物、激活剂和抑制剂的相互作用动态。此外，我们还探讨了创新的治疗方法，强调了该领域有前途的途径。
