S6K2

Ribosomal S6 kinase 2 (S6K2), also called S6 kinase beta-2, is a serine/threonine protein kinase in the ribosomal S6 kinase family. It is encoded by the RPS6KB2 gene in humans. S6K2 is one of two paralogous kinases, S6K1 and S6K2, that act as downstream effectors of the mTOR complex 1 (mTORC1) signaling pathway and contribute to the regulation of protein synthesis and cell growth.

Function and mechanism: S6K2 phosphorylates the ribosomal protein S6 and other translation-related substrates, thereby promoting translation initiation and ribosome biogenesis. Activation of S6K2 is driven by mTORC1-mediated phosphorylation at the hydrophobic motif, with additional activation by PDK1. Its activity reflects nutritional and growth cues and is subject to feedback regulation from the PI3K-AKT pathway.

Structure and expression: S6K2 contains the typical kinase catalytic domain and regulatory regions characteristic of the p70 S6 kinase family. Alternative splicing yields multiple isoforms, which may differ in localization and substrate engagement. S6K2 shows broad tissue expression, with variable abundance across tissues and cell types.

Clinical significance: Through its role in promoting protein synthesis, S6K2 contributes to normal cell growth and metabolism, but aberrant activation has been linked in some contexts to cancer progression and metabolic diseases. Because of its close relation to S6K1, S6K2 is considered a potential component of therapeutic strategies targeting dysregulated mTOR signaling.

See also: mTOR pathway, S6 kinase family, RPS6KB2.