Function
Ribosomal protein S6 kinase alpha 1 (RPS6KA1), also known as p90RSK, is a serine/threonine-protein kinase that plays a crucial role in cellular signaling pathways. It operates downstream of extracellular signal-regulated kinases (ERKs), specifically MAPK1/ERK2 and MAPK3/ERK1, mediating the activation of transcription factors like CREB1, ETV1/ER81, and NR4A1/NUR77 in response to mitogenic and stress stimuli. RPS6KA1 also regulates translation by phosphorylating RPS6 and EIF4B, influencing cellular processes such as proliferation, survival, and differentiation. Additionally, it modulates the mTOR signaling pathway by phosphorylating TSC2 and RPTOR, ultimately impacting cell growth and survival. Furthermore, RPS6KA1 directly phosphorylates the pro-apoptotic proteins BAD and DAPK1, inhibiting their pro-apoptotic function. In hepatic stellate cells, RPS6KA1 phosphorylates CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4), promoting cell survival. It also mediates the induction of hepatocyte proliferation by TGFA through CEBPB phosphorylation. RPS6KA1 is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, facilitating its association with 14-3-3 proteins and preventing its nuclear translocation. Finally, it phosphorylates EPHA2 at Ser-897, contributing to the RSK-EPHA2 signaling pathway that controls cell migration.