RSK3

RSK3 (ribosomal S6 kinase 3; RPS6KA2) is a serine/threonine kinase of the p90RSK family that contains two functional kinase domains and acts downstream of ERK/MAPK signaling to regulate cellular growth, differentiation, and transcriptional responses^[1][2]. Mechanistically, RSK3 integrates extracellular growth-factor signals through ERK-dependent activation and participates in MAPK-controlled signaling networks that influence gene expression and adaptive cellular programs^[1][3]. Through this position in the ERK pathway, RSK3 contributes to biological processes linked to cellular remodeling and stress responses, making it relevant for studies of signal transduction and kinase-regulated phenotypes^[2][3]. In disease-related models, RSK3 has been identified as a required mediator of pathological cardiac myocyte hypertrophy, and experimental evidence indicates that RSK3-dependent signaling modulates pathological myocardial growth and cardiac remodeling^[4][5]. Compared with related RSK isoforms, RSK3 possesses a unique N-terminal sequence that distinguishes it from other family members and has been associated with specific subcellular localization and signaling properties, supporting isoform-selective biological functions^[1]. This isoform-specific behavior is particularly important when dissecting ERK-effector pathways because phenotypes attributed to total RSK activity may depend on RSK3-mediated signaling mechanisms^[5]. For experimental applications, pharmacological targeting of the RSK family is widely used to interrogate ERK-RSK signaling, and RSK-directed inhibitors provide useful tools for studying RSK3-associated pathways in disease and cellular signaling models^[3].