RSK2 Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1. Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation. Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Expressed in many tissues, highest levels in skeletal muscle. Note: This description may include information from UniProtKB.
Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily
Chromosomal Location of Human Ortholog: Xq14
Cellular Component:  ribosome
Molecular Function:  ATP binding; cysteine-type endopeptidase inhibitor activity involved in apoptotic process; magnesium ion binding; protein kinase binding; protein serine/threonine kinase activity; ribosomal protein S6 kinase activity
Biological Process:  apoptotic process; intracellular signal transduction; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of transcription by RNA polymerase II; protein phosphorylation; response to lipopolysaccharide; toll-like receptor signaling pathway
Reference #:  NP_001178933 (RefSeq)
Alt. Names/Synonyms: RGD1563860; ribosomal protein S6 kinase A3; ribosomal protein S6 kinase alpha-3; ribosomal protein S6 kinase polypeptide 3; Rps6ka3; RSK2
Gene Symbols: Rps6ka3
Molecular weight: 83,724 Da
Basal Isoelectric point: 6.41  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  G2/M DNA Damage Checkpoint  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  Inhibition of Apoptosis  |  Microtubule Dynamics  |  Mitochondrial Control of Apoptosis  |  mTOR Signaling  |  Translation: eIF4E and p70S6K
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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RSK2

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Cross-references to other databases:  BioGPS  |  ENZYME  |  Entrez-Gene  |  GenPept  |  Ensembl Gene