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RPS6KA1 (ribosomal protein S6 kinase, 90kDa, polypeptide 1)

Written2008-03Philippe P Roux
Institute for Research in Immunology, Cancer (IRIC), Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montreal QC H3C 3J7, Canada

(Note : for Links provided by Atlas : click)


Alias (NCBI)HU-1
HGNC Alias symbRSK1
HGNC Previous nameribosomal protein S6 kinase, 90kD, polypeptide 1
LocusID (NCBI) 6195
Atlas_Id 43477
Location 1p36.11  [Link to chromosome band 1p36]
Location_base_pair Starts at 26529761 and ends at 26575025 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RPS6KA1.png]
Local_order Information about the local order of the human RPS6KA1 locus can be found at Human RPS6KA1 is found on chromosome 1, position 26,744,930-26,774,107, between genes coding for HMGN2 (High-mobility group nucleosome-binding domain-containing protein 2) and ARID1A (AT-rich interactive domain-containing protein 1A).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ARID1A (1p36.11)::RPS6KA1 (1p36.11)FGGY (1p32.1)::RPS6KA1 (1p36.11)RPS6KA1 (1p36.11)::LIN28A (1p36.11)
TMBIM6 (12q13.12)::RPS6KA1 (1p36.11)
Note The commonly used named for RPS6KA1 is RSK1, which will be used hereafter.


Note RSK1 was the first cloned isoform of the p90 ribosomal S6 kinase family, which now contains three other members (RSK2, RSK3 and RSK4).
Description The genomic size of the entire RSK1 gene is about 45,260 bp and is located on the + strand of chromosome 1. This gene contains 22 coding exons.
Transcription The length of the transcript is 3,186 bp, from which the open reading frame contains 2,208 bp. While the 5'UTR contains 154 bp, the 3'UTR contains 824 bp.
Pseudogene No human pseudogene known.


  The RSK1 protein contains two kinase domains separated by a linker region of about 100 aa. While the N-terminal kinase domain (NTKD) belongs to the AGC family of kinases, the C-terminal kinase domain (CTKD) belongs to the CaMK family. RSK1 activation requires its interaction with ERK1 and ERK2 through its C-terminal ERK docking region, which initiates an ordered phosphorylation sequence leading to the phosphorylation of six serine or threonine residues (S221, T359, S363, S380, T573 and S732).
Description The RSK1 protein consists of 735 amino acids, with an apparent molecular weight of about 85-90 kDa.
Expression Northern analyses and RNase protection assays revealed that RSK1 is expressed in many tissues, with higher levels in skeletal muscle, kidney, lung, liver, pancreas, spleen, thymus, and brain. Although other RSK isoforms are expressed ubiquitously in the brain, RSK1 is most abundant in the cerebellum. In situ hybridization of mouse embryonic tissues revealed that RSK1 is strongly expressed in regions harbouring highly proliferating cells. These include liver, lung, and thymus, as well as olfactory, respiratory, and gut epithelia.
Localisation RSK1 is normally present in the cytoplasm, but upon mitogenic stimulation it moves into the nucleus, where it phosphorylates several substrates involved in gene transcription. Within minutes of stimulation, RSK1 was shown to accumulate transiently at the plasma membrane, where it presumably receives additional inputs necessary for activation before nuclear translocation.
Function Mitogenic stimulation of the Ras/ERK pathway leads to the activation of RSK1. RSK1 seems to be a multifunctional ERK effector because it participates in various cellular processes, including nuclear signalling. RSK1 was found to regulate several transcription factors, including SRF, c-Fos, and Nur77. Additional nuclear factors have been shown to be regulated by RSK1, including MITF, estrogen receptor-a nuclear factor (NF)-ATc4 and ER81. RSK1 was shown to interact with the transcriptional coactivator CREB-binding protein (CBP), which, interestingly, binds many transcription factors known to be regulated by RSK1. On the basis of the nature of its substrates, RSK1 seems to have important functions in cellular growth control and proliferation. RSK1 may stimulate cell cycle progression through the regulation of immediate early gene products, such as c-Fos, which promotes the expression of cyclin D1 during the G0/G1 transition to S phase. Other proteins through which RSK1 may stimulate proliferation include the cyclin-dependent kinase (CDK) inhibitor p27kip1, the Na+/H+ exchanger NHE-1 and the kinase GSK3. RSK1 has been shown to phosphorylate and inhibit neuronal NO synthase in response to mitogenic signaling. RSK1 may also promote proliferation by regulating cell-growth-related protein synthesis. Indeed, RSK1 was shown to phosphorylate the tumour suppressor proteins TSC2 and LKB1, thereby resulting in increased mTOR signalling and mRNA translation.
Homology The RSK family contains four human isoforms (RSK1, RSK2, RSK3 and RSK4), which share 65-73% aa identity. RSK-related molecules have also been identified in C. elegans (T01H8.1) and D. melanogaster (RPS6-protein kinase-II), which share around 50% aa identity to human RSK1 and also contain the two kinase domains typical to RSK family members. No RSK homologues have been found in yeast or plant.


Somatic The natural variant K335T has been observed.

Implicated in

Entity Various cancers
Prognosis Frequent activation of the Ras/ERK signalling pathway has been reported in a broad range of human cancers including various carcinomas, glioblastomas and hematological malignancies. In some of these tumour types, RSK1 expression has been shown to be increased, such as in cancers of the breast and prostate.
Hyperactivation of RSK has been reported in multiple cancers. Activation of growth factor receptors either by ligand stimulation or receptor overexpression/mutation are common mechanisms that lead to RSK activation. RSK is now known to be a central player in a signalling pathway consisting of many components that have been implicated in tumorigenesis, including upstream Ras GTPases and Raf kinases.
Oncogenesis RSK1 is an important mediator of survival signals that protect cells from undergoing apoptosis and, thus, is a potentially important therapeutic target. Inhibition of RSK activity using the pharmacological inhibitor SL-0101 was shown to reduce the proliferation rates of breast cancer cells, but not normal breast epithelial cells.


Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase.
Alcorta DA, Crews CM, Sweet LJ, Bankston L, Jones SW, Erikson RL.
Mol Cell Biol 1989; 9: 3850-3859.
PMID 2779569
The Tumor Suppressor DAP Kinase Is a Target of RSK-Mediated Survival Signaling.
Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J.
Curr Biol 2005; 15: 1762-1767.
PMID 16213824
Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70-S6 kinase signaling systems are indicated by inhibition of protein synthesis.
Blenis J, Chung J, Erikson E, Alcorta DA, Erikson RL.
Cell Growth Differ 1991; 2: 279-285.
PMID 1648378
Subcellular localization and biological actions of activated RSK1 are determined by its interactions with subunits of cyclic AMP-dependent protein kinase.
Chaturvedi D, Poppleton HM, Stringfield T, Barbier A, Patel TB.
Mol Cell Biol 2006; 26: 4586-4600.
PMID 16738324
Nuclear localization and regulation of erk- and rsk-encoded protein kinases.
Chen RH, Sarnecki C, Blenis J.
Mol Cell Biol 1992; 12: 915-927.
PMID 1545823
Cytoplasmic to nuclear signal transduction by mitogen-activated protein kinase and 90 kDa ribosomal S6 kinase.
Chen RH, Tung R, Abate C, Blenis J.
Biochem Soc Trans 1993; 21: 895-900.
PMID 8132089
Phosphorylation of Cdc25C by pp90Rsk Contributes to a G(2) Cell Cycle Arrest in Xenopus Cycling Egg Extracts.
Chun J, Chau AS, Maingat FG, Edmonds SD, Ostergaard HL, Shibuya EK.
Cell Cycle. 2005 Jan;4(1):148-54.
PMID 15539959
A clickable inhibitor reveals context-dependent autoactivation of p90 RSK.
Cohen MS, Hadjivassiliou H, Taunton J.
Nat Chem Biol 2007; 3: 156-160.
PMID 17259979
Structural bioinformatics-based design of selective, irreversible kinase inhibitors.
Cohen MS, Zhang C, Shokat KM, Taunton J.
Science 2005; 308: 1318-1321.
PMID 15919995
Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK.
Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P.
J Biol Chem 1998; 273: 1496-1505.
PMID 9430688
Functional domains and phosphorylation of the orphan receptor Nur77.
Davis IL, Hazel TG, Chen R-H, Blenis J, Lau LF.
Molecular Endocrinology 1993; 7: 953-964.
PMID 8232315
p90Rsk is not involved in cytostatic factor arrest in mouse oocytes.
Dumont J, Umbhauer M, Rassinier P, Hanauer A, Verlhac MH.
J Cell Biol 2005; 169: 227-231.
PMID 15837801
Purification and characterization of a protein kinase from Xenopus eggs highly specific for ribosomal protein S6.
Erikson E, Maller JL.
J Biol Chem 1986; 261: 350-355.
PMID 3941081
Evidence for two catalytically active kinase domains in pp90rsk.
Fisher TL, Blenis J.
Mol Cell Biol 1996; 16: 1212-1219.
PMID 8622665
A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation.
Frodin M, Antal TL, Dummler BA, Jensen CJ, Deak M, Gammeltoft S, Biondi RM.
Embo J 2002; 21: 5396-5407.
PMID 12374740
A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1.
Frodin M, Jensen CJ, Merienne K, Gammeltoft S.
Embo J 2000; 19: 2924-2934.
PMID 10856237
Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization.
Fujita N, Sato S, Tsuruo T.
J Biol Chem 2003; 278: 49254-49260.
PMID 14504289
A p90(rsk) mutant constitutively interacting with MAP kinase uncouples MAP kinase from p34(cdc2)/cyclin B activation in Xenopus oocytes.
Gavin AC, Ni Ainle A, Chierici E, Jones M, Nebreda AR.
Mol Biol Cell 1999; 10: 2971-2986.
PMID 10473640
The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IkappaBalpha and stimulates its degradation in vitro.
Ghoda L, Lin X, Greene WC.
J Biol Chem 1997; 272: 21281-21288.
PMID 9261139
RSK and MSK in MAP kinase signalling.
Hauge C, Frodin M.
J Cell Sci 2006; 119: 3021-3023.
PMID 16868029
Differential localization of MAPK-activated protein kinases RSK1 and MSK1 in mouse brain.
Heffron D, Mandell JW.
Brain Res Mol Brain Res 2005; 136: 134-141.
PMID 15893597
Evidence that inactive p42 mitogen-activated protein kinase and inactive Rsk exist as a heterodimer in vivo.
Hsiao K-M, Chou S-Y, Shih S-J, Ferrell JE Jr.
Proc Natl Acad Sci USA 1994; 91: 5480-5484.
PMID 8202512
90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1.
Jensen CJ, Buch MB, Krag TO, Hemmings BA, Gammeltoft S, Frodin M.
J Biol Chem 1999; 274: 27168-27176.
PMID 10480933
pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167.
Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA.
Mol Cell Biol 1998; 18: 1978-1984.
PMID 9528769
Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development.
Kim M, Lee JH, Koh H, Lee SY, Jang C, Chung CJ, Sung JH, Blenis J, Chung J.
Embo J 2006; 25: 3056-3067.
PMID 16763554
Human rsk isoforms: cloning and characterization of tissue-specific expression.
Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M.
American Journal of Physiology 1994; 266: 351-359.
PMID 8141249
The signal-dependent coactivator CBP is a nuclear target for pp90RSK.
Nakajima T, Fukamizu A, Takahashi J, Gage FH, Fisher T, Blenis J, Montminy MR.
Cell 1996; 86: 465-474.
PMID 8756728
A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1.
Palmer A, Gavin AC, Nebreda AR.
Embo J 1998; 17: 5037-5047.
PMID 9724639
The S6KII (rsk) gene of Drosophila melanogaster differentially affects an operant and a classical learning task.
Putz G, Bertolucci F, Raabe T, Zars T, Heisenberg M.
J Neurosci 2004; 24: 9745-9751.
PMID 15525759
The MAP kinase ERK5 binds to and phosphorylates p90 RSK.
Ranganathan A, Pearson GW, Chrestensen CA, Sturgill TW, Cobb MH.
Arch Biochem Biophys 2006; 449: 8-16.
PMID 16626623
Characterization of regulatory events associated with membrane targeting of p90 ribosomal S6 kinase 1.
Richards SA, Dreisbach VC, Murphy LO, Blenis J.
Mol Cell Biol 2001; 21: 7470-7480.
PMID 11585927
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase.
Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J.
Proc Natl Acad Sci U S A 2004; 101: 13489-13494.
PMID 15342917
ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions.
Roux PP, Blenis J.
Microbiol Mol Biol Rev 2004; 68: 320-344.
PMID 15187187
Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.
Roux PP, Richards SA, Blenis J.
Mol Cell Biol 2003; 23: 4796-4804.
PMID 12832467
RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation.
Roux PP, Shahbazian D, Vu H, Holz MK, Cohen MS, Taunton J, Sonenberg N, Blenis J.
J Biol Chem 2007; 282: 14056-14064.
PMID 17360704
BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo.
Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, Grauert M, Hoffmann M, Schnapp G, Steegmaier M, Cohen P, Alessi DR.
Biochem J 2007; 401: 29-38.
PMID 17040210
IκBα is a target for the mitogen-activated 90 kDa ribosomal S6 kinase.
Schouten GJ, Vertegaal ACO, Whiteside ST, Israel A, Toebes M, Dorsman JC, van der Eb AJ, Zantema A.
EMBO J 1997; 16: 3133-3144.
PMID 9214631
Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation.
Schwab MS, Roberts BT, Gross SD, Tunquist BJ, Taieb FE, Lewellyn AL, Maller JL.
Curr Biol 2001; 11: 141-150.
PMID 11231148
The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity.
Shahbazian D, Roux PP, Mieulet V, Cohen MS, Raught B, Taunton J, Hershey JW, Blenis J, Pende M, Sonenberg N.
Embo J 2006; 25: 2781-2791.
PMID 16763566
Rsk1 mediates a MEK-MAP kinase cell survival signal.
Shimamura A, Ballif BA, Richards SA, Blenis J.
Curr Biol 2000; 10: 127-135.
PMID 10679322
Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo.
Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW.
J Biol Chem 1999; 274: 2893-2898.
PMID 9915826
p90 RSK-1 associates with and inhibits neuronal nitric oxide synthase.
Song T, Sugimoto K, Ihara H, Mizutani A, Hatano N, Kume K, Kambe T, Yamaguchi F, Tokuda M, Watanabe Y.
Biochem J 2007; 401: 391-398.
PMID 16984226
Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2.
Sutherland C, Alterio J, Campbell DG, Le Bourdelles B, Mallet J, Haavik J, Cohen P.
Eur J Biochem 1993; 217: 715-722.
PMID 7901013
p90(RSK) is a serum-stimulated Na+/H+ exchanger isoform-1 kinase. Regulatory phosphorylation of serine 703 of Na+/H+ exchanger isoform-1.
Takahashi E, Abe J, Gallis B, Aebersold R, Spring DJ, Krebs EG, Berk BC.
J Biol Chem 1999; 274: 20206-20214.
PMID 10400637
Identification of serine 380 as the major site of autophosphorylation of Xenopus pp90rsk.
Vik TA, Ryder JW.
Biochem Biophys Res Commun 1997; 235: 398-402.
PMID 9199205
Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase.
Wang X, Li W, Williams M, Terada N, Alessi DR, Proud CG.
Embo J 2001; 20: 4370-4379.
PMID 11500364
Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation.
Wingate AD, Campbell DG, Peggie M, Arthur JS.
Biochem J 2006; 393: 715-724.
PMID 16223362
Ribosomal S6 Kinase (RSK) Regulates Phosphorylation of Filamin A on an Important Regulatory Site.
Woo MS, Ohta Y, Rabinovitz I, Stossel TP, Blenis J.
Mol Cell Biol 2004; 24: 3025-3035.
PMID 15024089
Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex.
Yang TT, Xiong Q, Graef IA, Crabtree GR, Chow CW.
Mol Cell Biol 2005; 25: 907-920.
PMID 15657420
Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases.
Zhao Y, Bjorbaek C, Moller DE.
J Biol Chem 1996; 271: 29773-29779.
PMID 8939914


This paper should be referenced as such :
Roux, P P
RPS6KA1 (ribosomal protein S6 kinase, 90kDa, polypeptide 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(1):52-56.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)RPS6KA1   10430
Atlas Explorer : (Salamanque)RPS6KA1
Entrez_Gene (NCBI)RPS6KA1    ribosomal protein S6 kinase A1
RSK1; p90Rsk
GeneCards (Weizmann)RPS6KA1
Ensembl hg19 (Hinxton)ENSG00000117676 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000117676 [Gene_View]  ENSG00000117676 [Sequence]  chr1:26529761-26575025 [Contig_View]  RPS6KA1 [Vega]
ICGC DataPortalENSG00000117676
TCGA cBioPortalRPS6KA1
Genatlas (Paris)RPS6KA1
SOURCE (Princeton)RPS6KA1
Genetics Home Reference (NIH)RPS6KA1
Genomic and cartography
GoldenPath hg38 (UCSC)RPS6KA1  -     chr1:26529761-26575025 +  1p36.11   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RPS6KA1  -     1p36.11   [Description]    (hg19-Feb_2009)
GoldenPathRPS6KA1 - 1p36.11 [CytoView hg19]  RPS6KA1 - 1p36.11 [CytoView hg38]
Genome Data Viewer NCBIRPS6KA1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK092955 AK225672 AK292722 AK294818 AK299007
RefSeq transcript (Entrez)NM_001006665 NM_001330441 NM_002953
Consensus coding sequences : CCDS (NCBI)RPS6KA1
Gene ExpressionRPS6KA1 [ NCBI-GEO ]   RPS6KA1 [ EBI - ARRAY_EXPRESS ]   RPS6KA1 [ SEEK ]   RPS6KA1 [ MEM ]
Gene Expression Viewer (FireBrowse)RPS6KA1 [ Firebrowse - Broad ]
GenevisibleExpression of RPS6KA1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6195
GTEX Portal (Tissue expression)RPS6KA1
Human Protein AtlasENSG00000117676-RPS6KA1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)RPS6KA1
Human Protein Atlas [tissue]ENSG00000117676-RPS6KA1 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed218 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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