Ottawa Hospital Research Institute, Cancer Therapeutics, Ottawa, Ontario, K1H8L1, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, K1H8L6, Canada.
J Cell Sci. 2021 May 1;134(9). doi: 10.1242/jcs.258269. Epub 2021 May 7.
Over the past 20 years, the Ste20-like kinase (SLK; also known as STK2) has emerged as a central regulator of cytoskeletal dynamics. Reorganization of the cytoskeleton is necessary for a plethora of biological processes including apoptosis, proliferation, migration, tissue repair and signaling. Several studies have also uncovered a role for SLK in disease progression and cancer. Here, we review the recent findings in the SLK field and summarize the various roles of SLK in different animal models and discuss the biochemical mechanisms regulating SLK activity. Together, these studies have revealed multiple roles for SLK in coupling cytoskeletal dynamics to cell growth, in muscle repair and in negative-feedback loops critical for cancer progression. Furthermore, the ability of SLK to regulate some systems appears to be kinase activity independent, suggesting that it may be an important scaffold for signal transduction pathways. These various findings reveal highly complex functions and regulation patterns of SLK in development and disease, making it a potential therapeutic target.
在过去的 20 年中,丝氨酸/苏氨酸蛋白激酶 20 样激酶(SLK;也称为 STK2)已成为细胞骨架动力学的核心调节剂。细胞骨架的重排对于包括细胞凋亡、增殖、迁移、组织修复和信号转导在内的多种生物学过程是必需的。几项研究还揭示了 SLK 在疾病进展和癌症中的作用。在这里,我们综述了 SLK 领域的最新发现,并总结了 SLK 在不同动物模型中的各种作用,并讨论了调节 SLK 活性的生化机制。这些研究共同揭示了 SLK 在将细胞骨架动力学与细胞生长、肌肉修复以及对癌症进展至关重要的负反馈回路偶联中的多种作用。此外,SLK 调节某些系统的能力似乎与激酶活性无关,这表明它可能是信号转导途径的重要支架。这些不同的发现揭示了 SLK 在发育和疾病中的高度复杂的功能和调控模式,使其成为一个有潜力的治疗靶点。