Spirrison Ashley N, Lannigan Deborah A
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Expert Opin Ther Targets. 2024 Dec;28(12):1047-1059. doi: 10.1080/14728222.2024.2433123. Epub 2024 Dec 4.
The four members of the p90 ribosomal S6 kinase (RSK) family are serine/threonine protein kinases, which are phosphorylated and activated by ERK1/2. RSK1/2/3 are further phosphorylated by PDK1. Receiving inputs from two major signaling pathways places RSK as a key signaling node in numerous pathologies. A plethora of RSK1/2 substrates have been identified, and in the majority of cases the causative roles these RSK substrates play in the pathology are unknown.
The majority of studies have focused on RSK1/2 and their functions in a diverse group of cancers. However, RSK1/2 are known to have important functions in cardiovascular disease and neurobiological disorders. Based on the literature, we identified substrates that are common in these pathologies with the goal of identifying fundamental physiological responses to RSK1/2.
The core group of targets in pathologies driven by RSK1/2 are associated with the immune response. However, there is a paucity of the literature addressing RSK function in inflammation, which is critical to know as the pan RSK inhibitor, PMD-026, is entering phase II clinical trials for metastatic breast cancer. A RSK inhibitor has the potential to be used in numerous diverse diseases and disorders.
p90核糖体S6激酶（RSK）家族的四个成员是丝氨酸/苏氨酸蛋白激酶，它们被ERK1/2磷酸化并激活。RSK1/2/3进一步被PDK1磷酸化。接收来自两个主要信号通路的输入使RSK成为众多病理过程中的关键信号节点。已经鉴定出大量的RSK1/2底物，并且在大多数情况下，这些RSK底物在病理过程中所起的致病作用尚不清楚。
大多数研究集中在RSK1/2及其在多种癌症中的功能。然而，已知RSK1/2在心血管疾病和神经生物学疾病中具有重要功能。基于文献，我们鉴定了这些病理过程中常见的底物，目的是确定对RSK1/2的基本生理反应。
由RSK1/2驱动的病理过程中的核心靶点组与免疫反应相关。然而，关于RSK在炎症中的功能的文献很少，了解这一点至关重要，因为泛RSK抑制剂PMD-026正在进入转移性乳腺癌的II期临床试验。RSK抑制剂有可能用于多种不同的疾病和病症。
