RPS6KB1

RPS6KB1, or ribosomal protein S6 kinase beta-1, is a serine/threonine kinase in the AGC protein kinase family. In humans it acts as a key downstream effector of the PI3K-AKT-mTOR signaling axis. The protein S6K1 phosphorylates the ribosomal protein S6 and other targets to promote translation and ribosome biogenesis, thereby supporting cellular growth and protein synthesis in response to nutrients and growth factors.

The RPS6KB1 gene produces several isoforms, with two major translation-initiated products, p70-S6K1 and p85-S6K1, which differ in their regulatory regions but share the catalytic domain. Activation of S6K1 requires phosphorylation by mTORC1 at a hydrophobic motif (for example Thr389) and by PDK1 at the activation loop (for example Thr229), enabling full kinase activity. The protein is mainly cytoplasmic but can be recruited to membranes in response to signaling.

Key substrates include the S6 ribosomal protein (RPS6) and eIF4B, among others. Phosphorylation of S6 enhances translation of a subset of mRNAs, including many encoding components of the protein synthesis machinery. S6K1 also influences ribosome biogenesis, glucose metabolism, and lipogenesis, integrating nutrient status with growth.

Alterations in RPS6KB1 signaling have been linked to cancer and metabolic diseases. Overactivation of S6K1 can promote cell growth and survival, while inhibitors of mTOR/S6K1 signaling are explored in oncology. The gene is studied as part of signaling networks that coordinate growth, metabolism, and aging.