RSK1

RSK1 (RPS6KA1) is a serine/threonine kinase of the p90 ribosomal S6 kinase family that functions as a major downstream effector of the ERK1/2 signaling cascade and integrates mitogenic and stress-responsive signals into cellular responses regulating growth, differentiation, survival, and proliferation^[1][2]. Activation of RSK1 requires coordinated phosphorylation by ERK1/2 and PDK1, enabling substrate phosphorylation that influences transcription, translation, ribosome biogenesis, cytoskeletal regulation, and feedback control of MAPK signaling^[1][3]. Mechanistically, RSK1 occupies a central position within the Ras/Raf/MEK/ERK pathway and can phosphorylate multiple downstream targets involved in cell-cycle progression and cellular homeostasis, thereby linking extracellular stimulation to long-term biological outcomes^[1][4]. Aberrant RSK signaling has been associated with tumorigenesis, metastatic behavior, and therapy resistance in several cancer models, supporting the use of RSK1 as a mechanistic target in studies of oncogenic MAPK pathway activity^[1][5]. Compared with related isoforms, RSK family members display overlapping but nonredundant biological functions, and RSK1 is considered the most evolutionarily distinct member, with tissue-specific expression and signaling outputs that differ from those of RSK2, RSK3, and RSK4^[1]. For experimental applications, small-molecule inhibitors such as BI-D1870 and SL0101 have been widely used to interrogate RSK-dependent signaling; however, off-target effects have been reported, emphasizing the need for careful interpretation of pharmacological studies and for the development of more isoform-selective RSK inhibitors^[3][6].