Youn Minyoung, Gomez Jesus Omar, Mark Kailen, Sakamoto Kathleen M
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Biomedicines. 2021 Jun 24;9(7):726. doi: 10.3390/biomedicines9070726.
Ribosomal S6 Kinases (RSKs) are a group of serine/threonine kinases that function downstream of the Ras/Raf/MEK/ERK signaling pathway. Four RSK isoforms are directly activated by ERK1/2 in response to extracellular stimuli including growth factors, hormones, and chemokines. RSKs phosphorylate many cytosolic and nuclear targets resulting in the regulation of diverse cellular processes such as cell proliferation, survival, and motility. In hematological malignancies such as acute myeloid leukemia (AML), RSK isoforms are highly expressed and aberrantly activated resulting in poor outcomes and resistance to chemotherapy. Therefore, understanding RSK function in leukemia could lead to promising therapeutic strategies. This review summarizes the current information on human RSK isoforms and discusses their potential roles in the pathogenesis of AML and mechanism of pharmacological inhibitors.
核糖体S6激酶(RSKs)是一组丝氨酸/苏氨酸激酶,在Ras/Raf/MEK/ERK信号通路的下游发挥作用。四种RSK亚型可被ERK1/2直接激活,以响应包括生长因子、激素和趋化因子在内的细胞外刺激。RSKs使许多胞质和核靶点磷酸化,从而调节多种细胞过程,如细胞增殖、存活和运动。在急性髓系白血病(AML)等血液系统恶性肿瘤中,RSK亚型高度表达且异常激活,导致预后不良和化疗耐药。因此,了解RSK在白血病中的功能可能会带来有前景的治疗策略。本综述总结了关于人类RSK亚型的当前信息,并讨论了它们在AML发病机制中的潜在作用以及药理抑制剂的作用机制。