RPS6KA1

Ribosomal protein S6 kinase, 90kDa, polypeptide 1
Rendering based on PDB 2WNT​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2WNT​, 2Z7Q​, 2Z7R​, 2Z7S​, 3RNY​, 3TEI​, 4H3P​, 4NIF​
Identifiers
Symbols	RPS6KA1 ; HU-1; MAPKAPK1A; RSK; RSK1; p90Rsk
External IDs	OMIM: 601684 MGI: 104558 HomoloGene: 55703 ChEMBL: 2553 GeneCards: RPS6KA1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • magnesium ion binding • protein serine/threonine kinase activity • ribosomal protein S6 kinase activity • protein serine/threonine/tyrosine kinase activity • protein binding • ATP binding • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Cellular component • nucleus • nucleoplasm • cytoplasm • spindle • cytosol Biological process • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • cell cycle • signal transduction • synaptic transmission • axon guidance • positive regulation of cell growth • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • intracellular signal transduction • TRIF-dependent toll-like receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • negative regulation of apoptotic process • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • regulation of translation in response to stress • regulation of DNA-templated transcription in response to stress • innate immune response • positive regulation of cell differentiation • positive regulation of transcription from RNA polymerase II promoter • neurotrophin TRK receptor signaling pathway • stress-activated MAPK cascade • hepatocyte proliferation • positive regulation of hepatic stellate cell activation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6195	20111
Ensembl	ENSG00000117676	ENSMUSG00000003644
UniProt	Q15418	P18653
RefSeq (mRNA)	NM_001006665	NM_001285505
RefSeq (protein)	NP_001006666	NP_001272434
Location (UCSC)	Chr 1: 26.53 – 26.58 Mb	Chr 4: 133.85 – 133.89 Mb
PubMed search

Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.^[1]

Function

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical 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. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[2]

Interactions

RPS6KA1 has been shown to interact with:

• IκBα,^[3]
• MAPK1,^[4][5][6]
• TOB1^[7]
• TSC2,^[8][9] and
• YWHAB.^[10]

See also

• Ribosomal s6 kinase

References

1. Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M (Feb 1994). "Human rsk isoforms: cloning and characterization of tissue-specific expression". The American Journal of Physiology 266 (2 Pt 1): C351–9. PMID 8141249.
2. "Entrez Gene: RPS6KA1 ribosomal protein S6 kinase, 90kDa, polypeptide 1".
3. Schouten GJ, Vertegaal AC, Whiteside ST, Israël A, Toebes M, Dorsman JC, van der Eb AJ, Zantema A (Jun 1997). "IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase". The EMBO Journal 16 (11): 3133–44. doi:10.1093/emboj/16.11.3133. PMC 1169932. PMID 9214631.
4. Roux PP, Richards SA, Blenis J (Jul 2003). "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity". Molecular and Cellular Biology 23 (14): 4796–804. doi:10.1128/mcb.23.14.4796-4804.2003. PMC 162206. PMID 12832467.
5. Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM, Weber MJ (Apr 2003). "Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs". The Journal of Biological Chemistry 278 (17): 14926–35. doi:10.1074/jbc.M300485200. PMID 12594221.
6. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (Jan 1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". The Journal of Biological Chemistry 274 (5): 2893–8. doi:10.1074/jbc.274.5.2893. PMID 9915826.
7. Suzuki T, Matsuda S, Tsuzuku JK, Yoshida Y, Yamamoto T (Feb 2001). "A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob". Genes to Cells 6 (2): 131–8. doi:10.1046/j.1365-2443.2001.00406.x. PMID 11260258.
8. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (Sep 2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proceedings of the National Academy of Sciences of the United States of America 101 (37): 13489–94. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
9. Rolfe M, McLeod LE, Pratt PF, Proud CG (Jun 2005). "Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2)". The Biochemical Journal 388 (Pt 3): 973–84. doi:10.1042/BJ20041888. PMC 1183479. PMID 15757502.
10. Cavet ME, Lehoux S, Berk BC (May 2003). "14-3-3beta is a p90 ribosomal S6 kinase (RSK) isoform 1-binding protein that negatively regulates RSK kinase activity". The Journal of Biological Chemistry 278 (20): 18376–83. doi:10.1074/jbc.M208475200. PMID 12618428.

Further reading

• Chen RH, Sarnecki C, Blenis J (Mar 1992). "Nuclear localization and regulation of erk- and rsk-encoded protein kinases". Molecular and Cellular Biology 12 (3): 915–27. doi:10.1128/mcb.12.3.915. PMC 369523. PMID 1545823.
• Tratner I, Ofir R, Verma IM (Mar 1992). "Alteration of a cyclic AMP-dependent protein kinase phosphorylation site in the c-Fos protein augments its transforming potential". Molecular and Cellular Biology 12 (3): 998–1006. doi:10.1128/mcb.12.3.998. PMC 369532. PMID 1545828.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Chen RH, Abate C, Blenis J (Dec 1993). "Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase". Proceedings of the National Academy of Sciences of the United States of America 90 (23): 10952–6. doi:10.1073/pnas.90.23.10952. PMC 47899. PMID 8248197.
• Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME (Oct 1993). "A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity". Molecular and Cellular Biology 13 (10): 6260–73. doi:10.1128/mcb.13.10.6260. PMC 364685. PMID 8413226.
• Chen ZJ, Parent L, Maniatis T (Mar 1996). "Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity". Cell 84 (6): 853–62. doi:10.1016/S0092-8674(00)81064-8. PMID 8601309.
• Barge RM, de Koning JP, Pouwels K, Dong F, Löwenberg B, Touw IP (Mar 1996). "Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G-CSF-mediated activation of signaling complexes of the p21ras route". Blood 87 (6): 2148–53. PMID 8630373.
• Wong EV, Schaefer AW, Landreth G, Lemmon V (Jul 1996). "Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1". The Journal of Biological Chemistry 271 (30): 18217–23. doi:10.1074/jbc.271.30.18217. PMID 8663493.
• Xing J, Ginty DD, Greenberg ME (Aug 1996). "Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase". Science 273 (5277): 959–63. doi:10.1126/science.273.5277.959. PMID 8688081.
• Nakajima T, Fukamizu A, Takahashi J, Gage FH, Fisher T, Blenis J, Montminy MR (Aug 1996). "The signal-dependent coactivator CBP is a nuclear target for pp90RSK". Cell 86 (3): 465–74. doi:10.1016/S0092-8674(00)80119-1. PMID 8756728.
• Zhao Y, Bjorbaek C, Moller DE (Nov 1996). "Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases". The Journal of Biological Chemistry 271 (47): 29773–9. doi:10.1074/jbc.271.47.29773. PMID 8939914.
• Zaheer A, Lim R (Feb 1997). "Protein kinase A (PKA)- and protein kinase C-phosphorylated glia maturation factor promotes the catalytic activity of PKA". The Journal of Biological Chemistry 272 (8): 5183–6. doi:10.1074/jbc.272.8.5183. PMID 9030586.
• Schouten GJ, Vertegaal AC, Whiteside ST, Israël A, Toebes M, Dorsman JC, van der Eb AJ, Zantema A (Jun 1997). "IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase". The EMBO Journal 16 (11): 3133–44. doi:10.1093/emboj/16.11.3133. PMC 1169932. PMID 9214631.
• Li HL, Forman MS, Kurosaki T, Puré E (Jul 1997). "Syk is required for BCR-mediated activation of p90Rsk, but not p70S6k, via a mitogen-activated protein kinase-independent pathway in B cells". The Journal of Biological Chemistry 272 (29): 18200–8. doi:10.1074/jbc.272.29.18200. PMID 9218456.
• Chang YW, Traugh JA (Nov 1997). "Phosphorylation of elongation factor 1 and ribosomal protein S6 by multipotential S6 kinase and insulin stimulation of translational elongation". The Journal of Biological Chemistry 272 (45): 28252–7. doi:10.1074/jbc.272.45.28252. PMID 9353277.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• del Peso L, González-García M, Page C, Herrera R, Nuñez G (Oct 1997). "Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt". Science 278 (5338): 687–9. doi:10.1126/science.278.5338.687. PMID 9381178.
• Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P (Jan 1998). "Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK". The Journal of Biological Chemistry 273 (3): 1496–505. doi:10.1074/jbc.273.3.1496. PMID 9430688.
• Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA (Apr 1998). "pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167". Molecular and Cellular Biology 18 (4): 1978–84. doi:10.1128/mcb.18.4.1978. PMC 121427. PMID 9528769.