MSK1 Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury. Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: AGC group; EC 2.7.11.1; Kinase, protein; MSK subfamily; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family
Chromosomal Location of Human Ortholog: 14q32.11
Cellular Component:  cytoplasm; nucleoplasm; nucleus
Molecular Function:  ATP binding; magnesium ion binding; protein binding; protein kinase activity; protein serine/threonine kinase activity
Biological Process:  axon guidance; epidermal growth factor receptor signaling pathway; histone H2A-S1 phosphorylation; histone H3-S10 phosphorylation; histone H3-S28 phosphorylation; histone phosphorylation; inflammatory response; interleukin-1-mediated signaling pathway; intracellular signal transduction; negative regulation of cytokine production; negative regulation of transcription, DNA-templated; positive regulation of CREB transcription factor activity; positive regulation of histone acetylation; positive regulation of histone phosphorylation; positive regulation of NF-kappaB transcription factor activity; positive regulation of transcription by RNA polymerase II; protein phosphorylation; regulation of transcription, DNA-templated; stimulatory C-type lectin receptor signaling pathway
Reference #:  O75582 (UniProtKB)
Alt. Names/Synonyms: 90 kDa ribosomal protein S6 kinase 5; KS6A5; MGC1911; MSK1; MSPK1; Nuclear mitogen- and stress-activated protein kinase 1; ribosomal protein S6 kinase A5; Ribosomal protein S6 kinase alpha-5; ribosomal protein S6 kinase, 90kDa, polypeptide 5; RLPK; RPS6KA5; RSK-like protein kinase; RSKL; S6K-alpha-5
Gene Symbols: RPS6KA5
Molecular weight: 89,865 Da
Basal Isoelectric point: 6.63  Predict pI for various phosphorylation states
CST Pathways:  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  NF-kB Signaling  |  Regulation of P38 MAPKs
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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MSK1

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