Ribosomal protein S6 kinase alpha (RPS6KA)

Ribosomal protein S6 kinase alpha (RPS6KA), commonly known as the p90 ribosomal S6 kinase (RSK) family, consists of a group of highly conserved serine/threonine kinases that function as downstream effectors of the Ras-MAPK signaling pathway [1.2.1]. The family includes four human isoforms (RSK1-4) that are unique for containing two distinct, non-identical catalytic domains: an N-terminal kinase domain (NTKD) responsible for substrate phosphorylation and a C-terminal kinase domain (CTKD) involved in the activation of the NTKD [1.4.3]. RSKs play a critical role in regulating diverse cellular processes, including protein synthesis, cell growth, motility, and survival, by phosphorylating a wide range of substrates such as ribosomal protein S6, CREB, and the pro-apoptotic protein BAD [1.1.4, 1.4.4]. Dysregulation or overexpression of RPS6KA members is frequently observed in various malignancies, including breast, prostate, and lung cancers, where they contribute to tumor progression and drug resistance [1.1.1, 1.1.3]. Consequently, RPS6KA has emerged as a promising therapeutic target, with several small-molecule inhibitors currently in preclinical and early clinical development [1.4.1]. Additionally, mutations in the RPS6KA3 isoform are the primary cause of Coffin-Lowry syndrome, highlighting the protein's importance in neurodevelopment and cognitive function [1.4.2].

Other names

p90RSK90 kDa ribosomal protein S6 kinaseRSKMAPKAPK1Ribosomal S6 kinaseMAP kinase-activated protein kinase 1

Inhibition of the N-terminal or C-terminal kinase domains to block ATP binding and prevent the phosphorylation of downstream substrates in the MAPK/ERK signaling pathway.