RPS6KA1 explained

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

Further reading

• Chen RH, Sarnecki C, Blenis J . Nuclear localization and regulation of erk- and rsk-encoded protein kinases . Molecular and Cellular Biology . 12 . 3 . 915–27 . Mar 1992 . 1545823 . 369523 . 10.1128/mcb.12.3.915.
• Tratner I, Ofir R, Verma IM . 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 . Mar 1992 . 1545828 . 369532 . 10.1128/mcb.12.3.998.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Chen RH, Abate C, Blenis J . 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 . Dec 1993 . 8248197 . 47899 . 10.1073/pnas.90.23.10952 . 1993PNAS...9010952C . free .
• Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME . 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 . Oct 1993 . 8413226 . 364685 . 10.1128/mcb.13.10.6260.
• Chen ZJ, Parent L, Maniatis T . Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity . Cell . 84 . 6 . 853–62 . Mar 1996 . 8601309 . 10.1016/S0092-8674(00)81064-8 . 112412 . free .
• Barge RM, de Koning JP, Pouwels K, Dong F, Löwenberg B, Touw IP . 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 . Mar 1996 . 10.1182/blood.V87.6.2148.bloodjournal8762148 . 8630373 . free .
• Wong EV, Schaefer AW, Landreth G, Lemmon V . Involvement of p90rsk in neurite outgrowth mediated by the cell adhesion molecule L1 . The Journal of Biological Chemistry . 271 . 30 . 18217–23 . Jul 1996 . 8663493 . 10.1074/jbc.271.30.18217 . free .
• Xing J, Ginty DD, Greenberg ME . Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase . Science . 273 . 5277 . 959–63 . Aug 1996 . 8688081 . 10.1126/science.273.5277.959 . 1996Sci...273..959X . 22226803 .
• Nakajima T, Fukamizu A, Takahashi J, Gage FH, Fisher T, Blenis J, Montminy MR . The signal-dependent coactivator CBP is a nuclear target for pp90RSK . Cell . 86 . 3 . 465–74 . Aug 1996 . 8756728 . 10.1016/S0092-8674(00)80119-1 . free .
• Zhao Y, Bjorbaek C, Moller DE . Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases . The Journal of Biological Chemistry . 271 . 47 . 29773–9 . Nov 1996 . 8939914 . 10.1074/jbc.271.47.29773 . free .
• Zaheer A, Lim R . 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 . Feb 1997 . 9030586 . 10.1074/jbc.272.8.5183 . free .
• Schouten GJ, Vertegaal AC, Whiteside ST, Israël A, Toebes M, Dorsman JC, van der Eb AJ, Zantema A . IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase . The EMBO Journal . 16 . 11 . 3133–44 . Jun 1997 . 9214631 . 1169932 . 10.1093/emboj/16.11.3133 .
• Li HL, Forman MS, Kurosaki T, Puré E . 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 . Jul 1997 . 9218456 . 10.1074/jbc.272.29.18200 . free .
• Chang YW, Traugh JA . 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 . Nov 1997 . 9353277 . 10.1074/jbc.272.45.28252 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• del Peso L, González-García M, Page C, Herrera R, Nuñez G . Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt . Science . 278 . 5338 . 687–9 . Oct 1997 . 9381178 . 10.1126/science.278.5338.687 . 1997Sci...278..687D .
• Dalby KN, Morrice N, Caudwell FB, Avruch J, Cohen P . 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 . Jan 1998 . 9430688 . 10.1074/jbc.273.3.1496 . free .
• Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA . pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167 . Molecular and Cellular Biology . 18 . 4 . 1978–84 . Apr 1998 . 9528769 . 121427 . 10.1128/mcb.18.4.1978.

Notes and References

1. Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M . Human rsk isoforms: cloning and characterization of tissue-specific expression . The American Journal of Physiology . 266 . 2 Pt 1 . C351–9 . Feb 1994 . 8141249 . 10.1152/ajpcell.1994.266.2.C351.
2. Web site: 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 . IkappaB alpha is a target for the mitogen-activated 90 kDa ribosomal S6 kinase . The EMBO Journal . 16 . 11 . 3133–44 . Jun 1997 . 9214631 . 1169932 . 10.1093/emboj/16.11.3133 .
4. Roux PP, Richards SA, Blenis J . Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity . Molecular and Cellular Biology . 23 . 14 . 4796–804 . Jul 2003 . 12832467 . 162206 . 10.1128/mcb.23.14.4796-4804.2003.
5. Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM, Weber MJ . Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs . The Journal of Biological Chemistry . 278 . 17 . 14926–35 . Apr 2003 . 12594221 . 10.1074/jbc.M300485200 . free .
6. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW . 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 . Jan 1999 . 9915826 . 10.1074/jbc.274.5.2893. free .
7. Suzuki T, Matsuda S, Tsuzuku JK, Yoshida Y, Yamamoto T . A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob . Genes to Cells . 6 . 2 . 131–8 . Feb 2001 . 11260258 . 10.1046/j.1365-2443.2001.00406.x. free .
8. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J . 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 . Sep 2004 . 15342917 . 518784 . 10.1073/pnas.0405659101 . 2004PNAS..10113489R . free .
9. Rolfe M, McLeod LE, Pratt PF, Proud CG . 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 . Jun 2005 . 15757502 . 1183479 . 10.1042/BJ20041888 .
10. Cavet ME, Lehoux S, Berk BC . 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 . May 2003 . 12618428 . 10.1074/jbc.M208475200 . free .