Alternative titles; symbols
HGNC Approved Gene Symbol: RPS6KA4
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38) : 11:64,359,162-64,372,215 (from NCBI)
There are several subgroups of mitogen-activated protein kinases (MAPKs), including the extracellular signal-regulated kinases (ERKs) and the p38 protein family. To identify substrates of p38-alpha (600289), Pierrat et al. (1998) carried out a yeast 2-hybrid screen using p38-alpha as bait. The authors identified a partial placenta cDNA encoding ribosomal S6 kinase-B (RSKB). Using a combination of 5-prime RACE and library screening, they isolated an additional cDNA containing the entire RSKB coding region. The predicted 772-amino acid protein contains 2 complete catalytic ser/thr kinase domains, both of which include 11 consensus kinase subdomains and conserved ATP-binding and activation domains. The N-terminal and C-terminal kinase domains of RSKB and ribosomal protein kinase-1 (601684) share 53% and 43% identity, respectively. Northern blot analysis revealed that RSKB was widely expressed in tissues and cell lines.
Deak et al. (1998) isolated partial human and mouse cDNAs encoding RSKB, which they called mitogen- and stress-activated protein kinase-2 (MSK2). The predicted human MSK2 protein fragment is 75% identical to mitogen- and stress-activated protein kinase-1 (603607).
Pierrat et al. (1998) found that RSKB was a p38-alpha substrate and was activated by p38-alpha and, more weakly, by ERK1 (601795). Both cAMP response element-binding protein (CREB; see CREB1, 123810) and c-fos (164810) were phosphorylated by RSKB in vitro. Reporter gene assays demonstrated that RSKB controlled CREB and activator protein-1 (165160) activities in vivo. RSKB localized to the nucleus and cotranslocated p38-alpha.
Gross (2014) mapped the RPS6KA4 gene to chromosome 11q13.1 based on an alignment of the RPS6KA4 sequence (GenBank BC047896) with the genomic sequence (GRCh37).
Deak, M., Clifton, A. D., Lucocq, J. M., Alessi, D. R. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 17: 4426-4441, 1998. [PubMed: 9687510] [Full Text: https://doi.org/10.1093/emboj/17.15.4426]
Gross, M. B. Personal Communication. Baltimore, Md. 5/14/2014.
Pierrat, B., Correia, J. S., Mary, J.-L., Tomas-Zuber, M., Lesslauer, W. RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38-alpha mitogen-activated protein kinase (p38-alpha-MAPK). J. Biol. Chem. 273: 29661-29671, 1998. [PubMed: 9792677] [Full Text: https://doi.org/10.1074/jbc.273.45.29661]