RSK2

RSK2 (ribosomal S6 kinase 2, RPS6KA3) is a widely expressed serine/threonine kinase of the p90RSK family that functions downstream of ERK1/2 and phosphoinositide-dependent kinase 1, positioning it as a critical effector of MAPK signaling that regulates cell survival, proliferation, and transcriptional responses^[1][2]. RSK2 integrates extracellular growth-factor signals into intracellular phosphorylation events and contributes to the control of cell-cycle progression and transformation-associated programs through phosphorylation of downstream substrates^[1][3]. Mechanistically, RSK2 participates in RAS-MAPK pathway regulation and influences phosphorylation of signaling and transcriptional regulators, thereby affecting cellular growth and adaptive responses^[2][4]. In disease-relevant models, genetic deletion or knockdown of RSK2 suppresses cell proliferation, induces G1-phase accumulation, and reduces oncogenic transformation, whereas increased RSK2 activity promotes tumor-promoter-induced cell transformation and cancer-related phenotypes^[1][5]. RSK2 is also clinically significant because loss-of-function mutations in RPS6KA3 cause Coffin-Lowry syndrome, linking RSK2-dependent signaling to neurodevelopmental and skeletal abnormalities^[6][7]. Compared with related RSK isoforms, RSK2 has been identified as a specific binding partner of SPRED2, revealing isoform-selective regulation within the RAS-MAPK network and highlighting functional distinctions that are not shared uniformly across the RSK family^[2]. For experimental applications, pharmacological inhibitors including kaempferol and the RSK inhibitor BI-D1870 have been used to suppress RSK-dependent signaling, making RSK2 a valuable target for mechanistic studies of MAPK-driven proliferation, transformation, and therapeutic intervention strategies^[1][4].