Ribosomal protein S6 kinase alpha-3 (RSK2) (RSK2)

Ribosomal protein S6 kinase alpha-3 (RSK2), also known as MAPK-activated protein kinase 1b, is a member of the 90 kDa ribosomal S6 kinase (p90RSK) family of serine/threonine kinases [1]. It serves as a critical downstream effector of the Ras-ERK signaling pathway, integrating extracellular signals to regulate diverse cellular processes including growth, proliferation, survival, and motility [1, 3]. RSK2 is structurally unique, possessing two distinct kinase domains: an N-terminal kinase domain (NTKD) responsible for substrate phosphorylation and a C-terminal kinase domain (CTKD) that regulates the NTKD [1]. Mutations in the RPS6KA3 gene, which encodes RSK2, are the primary cause of Coffin-Lowry syndrome, a rare X-linked disorder characterized by intellectual disability and skeletal abnormalities [2, 4]. In oncology, RSK2 is frequently overexpressed or hyperactivated in various malignancies, such as breast, lung, and prostate cancers, where it promotes tumor progression and resistance to therapy [3]. Consequently, RSK2 has emerged as a promising therapeutic target, with small-molecule inhibitors like PMD-026 being evaluated in clinical trials for their potential to disrupt oncogenic signaling [5].

Other names

MAPK-activated protein kinase 1bMAPKAP-K1bp90RSK2RPS6KA390 kDa ribosomal protein S6 kinase 3pp90RSK2Ribosomal S6 kinase 2

ATP-competitive or covalent inhibition of the N-terminal kinase domain (NTKD) or C-terminal kinase domain (CTKD) to block downstream phosphorylation of substrates [1, 3, 5].