Ribosomal protein S6 kinase (RSK) and Mitogen- and stress-activated kinase (MSK) (RSK/MSK)

Ribosomal protein S6 kinases (RSKs) and mitogen- and stress-activated kinases (MSKs) are closely related serine/threonine protein kinases that act as downstream effector nodes in the mitogen-activated protein kinase (MAPK) signaling cascade, particularly following extracellular signal-regulated kinase (ERK) and, for MSK, also p38 MAPK activation[1][2][5][7]. RSKs (RSK1-4) and MSKs (MSK1/2) regulate a broad range of cellular processes, including cell growth, survival, proliferation, motility, and transcription, by phosphorylating numerous cytosolic and nuclear substrates. Their activity links them to diverse human diseases, most notably cancer (where aberrant Ras-MAPK-ERK pathway activation is common), as well as inflammation, cardiovascular, and neurodegenerative conditions[2][4][5][6]. Both RSK and MSK isoforms have distinct but also overlapping biological functions, and their kinase activity can regulate oncogenic transcription factors (like NF-κB, CREB, ERα) and impact tumor growth and survival[2][4][5]. Multiple isoform- and pan-family inhibitors are under investigation as cancer therapeutics, but therapeutic development is complicated by the need for family selectivity and by the broad roles these kinases play in essential cellular functions[4][6][8].

Other names

p90 ribosomal S6 kinase (p90RSK)Mitogen- and stress-activated protein kinaseMAPK-activated protein kinase 1 (MAPKAP-K1; for RSK)MSK1, MSK2 (for MSK isoforms)RSK1, RSK2, RSK3, RSK4 (for RSK isoforms)

Inhibition of kinase catalytic activity, blocking phosphorylation of downstream substrates[4][8] - Cell cycle arrest and induction of apoptosis via suppression of survival pathways[8] - Suppression of transcription factor activation (e.g., inhibition of NF-κB, CREB, or ERα phosphorylation)[4]