バックグラウンド: | 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 (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration. |
シノニム: | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2), RPS6KA3, ISPK1 MAPKAPK1B RSK2 |
UniProt Protein Function: | RSK2: an AGC kinase of the RSK family. Phosphorylated and activated by Erk1 and -2 in response to many growth factors, polypeptide hormones and neurotransmitters. Several phosphorylation sites are important for its activation. Possesses two kinase domains connected by a regulator linker region. Phosphorylates a wide range of substrates including ribosomal protein S6. Prominently expressed in brain structures essential for cognitive function and learning. |
UniProt Protein Details: | Protein type:Kinase, protein; Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; Protein kinase, AGC; AGC group; RSK family; RSK subfamily Chromosomal Location of Human Ortholog: Xp22.2-p22.1 Cellular Component: cytoplasm; cytosol; nucleoplasm; nucleus Molecular Function:caspase inhibitor activity; kinase activity; protein binding; protein kinase activity; protein serine/threonine kinase activity Biological Process: central nervous system development; negative regulation of apoptosis; negative regulation of caspase activity; positive regulation of cell differentiation; positive regulation of cell growth; positive regulation of transcription from RNA polymerase II promoter; regulation of transcription in response to stress; regulation of translation in response to stress; response to lipopolysaccharide; signal transduction; skeletal development; toll-like receptor signaling pathway Disease: Coffin-lowry Syndrome; Mental Retardation, X-linked 19 |
NCBI Summary: | This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS). [provided by RefSeq, Jul 2008] |
UniProt Code: | P51812 |
NCBI GenInfo Identifier: | 1730070 |
NCBI Gene ID: | 6197 |
NCBI Accession: | P51812.1 |
UniProt Secondary Accession: | P51812,Q4VAP3, Q59H26, Q5JPK8, Q7Z3Z7, B2R9V4, |
UniProt Related Accession: | P51812 |
Molecular Weight: | 83,736 Da |
NCBI Full Name: | Ribosomal protein S6 kinase alpha-3 |
NCBI Synonym Full Names: | ribosomal protein S6 kinase A3 |
NCBI Official Symbol: | RPS6KA3 |
NCBI Official Synonym Symbols: | CLS; RSK; HU-3; RSK2; MRX19; ISPK-1; p90-RSK2; pp90RSK2; MAPKAPK1B; S6K-alpha3 |
NCBI Protein Information: | ribosomal protein S6 kinase alpha-3 |
UniProt Protein Name: | Ribosomal protein S6 kinase alpha-3 |
UniProt Synonym Protein Names: | 90 kDa ribosomal protein S6 kinase 3; p90-RSK 3; p90RSK3; Insulin-stimulated protein kinase 1; ISPK-1; MAP kinase-activated protein kinase 1b; MAPK-activated protein kinase 1b; MAPKAP kinase 1b; MAPKAPK-1b; Ribosomal S6 kinase 2; RSK-2; pp90RSK2 |
Protein Family: | Ribosomal protein S6 kinase |
UniProt Gene Name: | RPS6KA3 |
UniProt Entry Name: | KS6A3_HUMAN |