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Gene Review

Rps6ka1  -  ribosomal protein S6 kinase polypeptide 1

Mus musculus

Synonyms: 90 kDa ribosomal protein S6 kinase 1, MAP kinase-activated protein kinase 1a, MAPK-activated protein kinase 1a, MAPKAP kinase 1a, MAPKAPK-1a, ...
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Disease relevance of Rps6ka1

  • To confirm the role of p90RSK in cTnI phosphorylation in vivo, we generated adenovirus containing a dominant negative form of p90RSK (Ad-DN-p90RSK) [1].
  • Apoptosis induced by 12 hours of anoxia followed by 24 hours' reoxygenation was significantly reduced in cells expressing Ad.DN-RSK (18.6+/-2.0%) compared with Ad.LacZ (29.3+/-5.4%) [2].
  • Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning [3].
  • Evidence of coordinate regulation of virulence in Salmonella typhimurium involving the rsk element of the 95-kilobase plasmid [4].

High impact information on Rps6ka1

  • MAP kinases may participate in protein kinase cascades that link Src family protein-tyrosyl kinases to seryl-threonyl kinases such as those encoded by rsk and raf, which are putative substrates of MAP kinases [5].
  • Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases [6].
  • The responder gene has been identified as a fusion gene formed from a sperm motility kinase and a ribosomal S6 kinase [7].
  • The S6K and RSK proteins are members of the AGC protein kinase family, and require PDK1 phosphorylation for activation [8].
  • The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics [8].

Biological context of Rps6ka1

  • However, in contrast to S6K, RSK and SGK, hydrophobic motif phosphorylation of these enzymes is not thought to control their activation by PDK1 [9].
  • The expression of cyclin B1 and the phosphorylation of MAPK/p90rsk could still be detected in ALLN or MG-132-treated oocytes even at 8 h after parthenogenetic activation or insemination, which may account for the inhibition of PB2 emission and pronuclear formation [10].
  • The injection of constitutively active mutant forms of Rsk1 and Rsk2 does not induce a cell cycle arrest in two-cell mouse embryos [11].
  • We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK [12].
  • Interestingly, however, the expression of transfected raf oncogenes did not induce MAPK or RSK activation, and the insulin-induced activation of these kinases was not blocked by expression of transfected dominant negative raf mutants [13].

Anatomical context of Rps6ka1


Associations of Rps6ka1 with chemical compounds


Enzymatic interactions of Rps6ka1

  • Finally, RANTES treatment induces nuclear translocation of phosphorylated RSK in astrocytes [22].
  • In vitro, both RSK kinases and MBP kinase phosphorylated recombinant RSK and generated nearly identical two-dimensional tryptic phosphopeptide maps [23].
  • We also found that p90 RSK directly phosphorylates CREB on Ser-133 following BCR cross-linking and is positioned downstream of nPKCdelta [24].

Regulatory relationships of Rps6ka1


Other interactions of Rps6ka1


Analytical, diagnostic and therapeutic context of Rps6ka1


  1. Role of p90 ribosomal S6 kinase (p90RSK) in reactive oxygen species and protein kinase C beta (PKC-beta)-mediated cardiac troponin I phosphorylation. Itoh, S., Ding, B., Bains, C.P., Wang, N., Takeishi, Y., Jalili, T., King, G.L., Walsh, R.A., Yan, C., Abe, J. J. Biol. Chem. (2005) [Pubmed]
  2. Inhibiting p90 ribosomal S6 kinase prevents (Na+)-H+ exchanger-mediated cardiac ischemia-reperfusion injury. Maekawa, N., Abe, J., Shishido, T., Itoh, S., Ding, B., Sharma, V.K., Sheu, S.S., Blaxall, B.C., Berk, B.C. Circulation (2006) [Pubmed]
  3. Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning. Zeniou, M., Ding, T., Trivier, E., Hanauer, A. Hum. Mol. Genet. (2002) [Pubmed]
  4. Evidence of coordinate regulation of virulence in Salmonella typhimurium involving the rsk element of the 95-kilobase plasmid. Vandenbosch, J.L., Kurlandsky, D.R., Urdangaray, R., Jones, G.W. Infect. Immun. (1989) [Pubmed]
  5. Tyrosyl phosphorylation and activation of MAP kinases by p56lck. Ettehadieh, E., Sanghera, J.S., Pelech, S.L., Hess-Bienz, D., Watts, J., Shastri, N., Aebersold, R. Science (1992) [Pubmed]
  6. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Zhao, J., Yuan, X., Frödin, M., Grummt, I. Mol. Cell (2003) [Pubmed]
  7. Transmission ratio distortion in mice. Lyon, M.F. Annu. Rev. Genet. (2003) [Pubmed]
  8. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. Shahbazian, D., Roux, P.P., Mieulet, V., Cohen, M.S., Raught, B., Taunton, J., Hershey, J.W., Blenis, J., Pende, M., Sonenberg, N. EMBO J. (2006) [Pubmed]
  9. In vivo role of the phosphate groove of PDK1 defined by knockin mutation. Collins, B.J., Deak, M., Murray-Tait, V., Storey, K.G., Alessi, D.R. J. Cell. Sci. (2005) [Pubmed]
  10. Ubiquitin-proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation. Huo, L.J., Fan, H.Y., Zhong, Z.S., Chen, D.Y., Schatten, H., Sun, Q.Y. Mech. Dev. (2004) [Pubmed]
  11. p90Rsk is not involved in cytostatic factor arrest in mouse oocytes. Dumont, J., Umbhauer, M., Rassinier, P., Hanauer, A., Verlhac, M.H. J. Cell Biol. (2005) [Pubmed]
  12. Essential role of PDK1 in regulating cell size and development in mice. Lawlor, M.A., Mora, A., Ashby, P.R., Williams, M.R., Murray-Tait, V., Malone, L., Prescott, A.R., Lucocq, J.M., Alessi, D.R. EMBO J. (2002) [Pubmed]
  13. Dissociation between activation of Raf-1 kinase and the 42-kDa mitogen-activated protein kinase/90-kDa S6 kinase (MAPK/RSK) cascade in the insulin/Ras pathway of adipocytic differentiation of 3T3 L1 cells. Porras, A., Muszynski, K., Rapp, U.R., Santos, E. J. Biol. Chem. (1994) [Pubmed]
  14. Light- and clock-dependent regulation of ribosomal S6 kinase activity in the suprachiasmatic nucleus. Butcher, G.Q., Lee, B., Hsieh, F., Obrietan, K. Eur. J. Neurosci. (2004) [Pubmed]
  15. MEK, ERK, and p90RSK are present on mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit. Willard, F.S., Crouch, M.F. Cell. Signal. (2001) [Pubmed]
  16. 14-3-3beta is a p90 ribosomal S6 kinase (RSK) isoform 1-binding protein that negatively regulates RSK kinase activity. Cavet, M.E., Lehoux, S., Berk, B.C. J. Biol. Chem. (2003) [Pubmed]
  17. Insulin stimulation of mitogen-activated protein kinase, p90rsk, and p70 S6 kinase in skeletal muscle of normal and insulin-resistant mice. Implications for the regulation of glycogen synthase. Chang, P.Y., Le Marchand-Brustel, Y., Cheatham, L.A., Moller, D.E. J. Biol. Chem. (1995) [Pubmed]
  18. Urea activates ribosomal S6 kinase (RSK) in a MEK-dependent fashion in renal mIMCD3 cells. Zhang, Z., Cohen, D.M. Am. J. Physiol. (1998) [Pubmed]
  19. Increased histone acetyltransferase and lysine acetyltransferase activity and biphasic activation of the ERK/RSK cascade in insular cortex during novel taste learning. Swank, M.W., Sweatt, J.D. J. Neurosci. (2001) [Pubmed]
  20. Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. Hao, Y., Creson, T., Zhang, L., Li, P., Du, F., Yuan, P., Gould, T.D., Manji, H.K., Chen, G. J. Neurosci. (2004) [Pubmed]
  21. The inhaled anesthetic, isoflurane, enhances Ca2+-dependent survival signaling in cortical neurons and modulates MAP kinases, apoptosis proteins and transcription factors during hypoxia. Bickler, P.E., Fahlman, C.S. Anesth. Analg. (2006) [Pubmed]
  22. RANTES-mediated chemokine transcription in astrocytes involves activation and translocation of p90 ribosomal S6 protein kinase (RSK). Zhang, Y., Zhai, Q., Luo, Y., Dorf, M.E. J. Biol. Chem. (2002) [Pubmed]
  23. Mitogen-activated Swiss mouse 3T3 RSK kinases I and II are related to pp44mpk from sea star oocytes and participate in the regulation of pp90rsk activity. Chung, J., Pelech, S.L., Blenis, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. B cell receptor-induced cAMP-response element-binding protein activation in B lymphocytes requires novel protein kinase Cdelta. Blois, J.T., Mataraza, J.M., Mecklenbraüker, I., Tarakhovsky, A., Chiles, T.C. J. Biol. Chem. (2004) [Pubmed]
  25. Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. Eldar-Finkelman, H., Seger, R., Vandenheede, J.R., Krebs, E.G. J. Biol. Chem. (1995) [Pubmed]
  26. Involvement of phosphatidylinositol 3-kinase in the mediation of erythropoietin-induced activation of p70S6k. Jaster, R., Bittorf, T., Brock, J. Cell. Signal. (1997) [Pubmed]
  27. Ribosomal S6 kinase p90rsk and mRNA cap-binding protein eIF4E phosphorylations correlate with MAP kinase activation during meiotic reinitiation of mouse oocytes. Gavin, A.C., Schorderet-Slatkine, S. Mol. Reprod. Dev. (1997) [Pubmed]
  28. Activation of mitogen-activated protein kinase cascade and phosphorylation of cytoskeletal proteins after neurone-specific activation of p21ras. I. Mitogen-activated protein kinase cascade. Holzer, M., Gärtner, U., Klinz, F.J., Narz, F., Heumann, R., Arendt, T. Neuroscience (2001) [Pubmed]
  29. Ribosomal S6 kinase as a mediator of keratinocyte growth factor-induced activation of Akt in epithelial cells. Pan, Z.Z., Devaux, Y., Ray, P. Mol. Biol. Cell (2004) [Pubmed]
  30. Activation of p70 S6 kinase and erk-encoded mitogen-activated protein kinases is resistant to high cyclic nucleotide levels in Swiss 3T3 fibroblasts. Petritsch, C., Woscholski, R., Edelmann, H.M., Ballou, L.M. J. Biol. Chem. (1995) [Pubmed]
  31. Regulation of the CREB signaling cascade in the visual cortex by visual experience and neuronal activity. Suzuki, S., al-Noori, S., Butt, S.A., Pham, T.A. J. Comp. Neurol. (2004) [Pubmed]
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