RPS6KA4

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 CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene.

Full Name

RIBOSOMAL PROTEIN S6 KINASE A4

Function

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 factor RELA, 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. 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.

Biological Process

Biological Process histone phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process inflammatory responseIEA:UniProtKB-KW
Biological Process interleukin-1-mediated signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process intracellular signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of cytokine productionManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process peptidyl-serine phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of CREB transcription factor activityManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of histone acetylationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of histone phosphorylationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process post-translational protein modificationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Nucleus

PTM

Ser-343 and Thr-568 phosphorylation is required for kinase activity. Ser-343 and Ser-196 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).