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RPS6KA3  -  ribosomal protein S6 kinase, 90kDa,...

Homo sapiens

Synonyms: 90 kDa ribosomal protein S6 kinase 3, CLS, HU-3, ISPK-1, ISPK1, ...
 
 
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Disease relevance of RPS6KA3

 

Psychiatry related information on RPS6KA3

  • However, in one family (MRX19), a missense mutation was associated solely with mild mental retardation and no other clinical feature [2].
  • Expression of the RSK2 gene during early human development [6].
  • A statistically significant difference in learning the skills was observed between CLS/MT majors and non-CLS/MT majors for the following skills: problem solving, correlating data, precision studies, research, analytical reasoning, and troubleshooting [7].
 

High impact information on RPS6KA3

 

Chemical compound and disease context of RPS6KA3

  • Patients with the X-linked disorder Coffin-Lowry syndrome (CLS) have cognitive disabilities, distinctive features, and bony abnormalities as well as mutations in RSK2 (ribosomal S6 kinase-2), a protein kinase that activates CREB by phosphorylation at serine 133 [11].
  • The 90 kDa ribosomal S6 serine/threonine kinase 2 gene (RSK2, U08316) has been recently identified as a disease-causing gene in an X-linked disorder, the Coffin-Lowry Syndrome (MIM 303600) characterized by severe mental retardation, facial dysmorphisms and progressive skeletal malformations [6].
  • Only 1 of 5 African Burkitt's lymphoma CLS and 2 of 7 EBV- CLS expressed IL-7 [12].
  • Data from the completed "Suppression of Atrial Fibrillation by DDD+ Overdrive Pacing with Inos2 CLS (closed-loop system) Pacemakers" multicenter trial were retrospectively evaluated to examine the influence of concomitant antiarrhythmic drugs on the clinical success of conventional single site right atrial overdrive pacing compared with DDD pacing [13].
  • Calcium dobesilate (CLS 2210) protects the myocardium in early acute myocardial infarction: a preliminary randomized, double-blind, placebo-controlled study of its effects on biochemical markers [14].
 

Biological context of RPS6KA3

  • PEA-15 expression also blocks histone H3 phosphorylation, an RSK2-dependent event that may contribute to effects on gene expression [15].
  • These findings underscore the importance of the Rsk2 isozyme in the M phase functions of p42 MAP kinase and provide tools for further examining Rsk2 function [16].
  • 3 At physiological [ATP] (5 mM), both GF109203X and Ro31-8220 exhibited reduced potency as inhibitors of RSK2, PKCalpha and PKCepsilon (IC50 values of 7400, 310 and 170 nM, respectively, for GF109203X, and 930, 150 and 140 nM, respectively, for Ro31-8220), with the latter agent retaining its relatively greater potency [17].
  • We propose a model in which dynamic formation and dissociation of the CBP-RSK2 complex in response to mitogenic stimulation allow regulated phosphorylation and acetylation of specific substrates, leading to coordinated modulation of gene expression [18].
  • Transfection of a dominant-negative form of RSK2 (DN RSK2) partly blocked the anti-apoptosis effect of bFGF in irradiated HUVECs [19].
 

Anatomical context of RPS6KA3

 

Associations of RPS6KA3 with chemical compounds

 

Physical interactions of RPS6KA3

  • Furthermore, purified PEA-15 bound in vitro translated RSK2, suggesting that these proteins interact directly [15].
 

Enzymatic interactions of RPS6KA3

  • The localization of RSK4 in the interval that is commonly deleted in mentally retarded males together with the high degree of amino acid identity with RSK2 suggests that RSK4 plays a role in normal neuronal development [28].
  • Phosphoserine was recovered by the phosphoamino acid analysis of MRLC phosphorylated by RSK-2 [29].
 

Regulatory relationships of RPS6KA3

 

Other interactions of RPS6KA3

  • Both dephosphorylated (from quiescent cells) and phosphorylated (from stimulated cells) MAPKs were associated with RSK2 and RSK3 [30].
  • Mutational analysis of ribosomal S6 kinase 2 shows differential regulation of its kinase activity from that of ribosomal S6 kinase 1 [31].
  • These results can be attributed to two effects of PEA-15 on RSK2 [15].
  • The RSK2 regulation of PSA expression occurred via a mechanism involving both RSK2 kinase activity and its ability to associate with the coactivator, p300 [32].
  • We show that this interaction has functional consequences including the inhibition of RSK2-dependent CREB transcription [15].
 

Analytical, diagnostic and therapeutic context of RPS6KA3

References

  1. Activation of RSK by UV-light: phosphorylation dynamics and involvement of the MAPK pathway. Mérienne, K., Jacquot, S., Zeniou, M., Pannetier, S., Sassone-Corsi, P., Hanauer, A. Oncogene (2000) [Pubmed]
  2. X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1). Jacquot, S., Zeniou, M., Touraine, R., Hanauer, A. Eur. J. Hum. Genet. (2002) [Pubmed]
  3. Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. Kim, Y.B., Kotani, K., Ciaraldi, T.P., Henry, R.R., Kahn, B.B. Diabetes (2003) [Pubmed]
  4. A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome. Touraine, R.L., Zeniou, M., Hanauer, A. Eur. J. Pediatr. (2002) [Pubmed]
  5. Differential expression genes analyzed by cDNA array in the regulation of rat hepatic fibrogenesis. Qiang, H., Lin, Y., Zhang, X., Zeng, X., Shi, J., Chen, Y.X., Yang, M.F., Han, Z.G., Xie, W.F. Liver Int. (2006) [Pubmed]
  6. Expression of the RSK2 gene during early human development. Guimiot, F., Delezoide, A.L., Hanauer, A., Simonneau, M. Gene Expr. Patterns (2004) [Pubmed]
  7. The learning and application of generic skills by CLSs/MTs who have 'left the field'. Guiles, H.J., Tatum, D.S. Clinical laboratory science : journal of the American Society for Medical Technology. (2002) [Pubmed]
  8. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H.C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T.M., Hanauer, A., Karsenty, G. Cell (2004) [Pubmed]
  9. A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation. Merienne, K., Jacquot, S., Pannetier, S., Zeniou, M., Bankier, A., Gecz, J., Mandel, J.L., Mulley, J., Sassone-Corsi, P., Hanauer, A. Nat. Genet. (1999) [Pubmed]
  10. Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Sassone-Corsi, P., Mizzen, C.A., Cheung, P., Crosio, C., Monaco, L., Jacquot, S., Hanauer, A., Allis, C.D. Science (1999) [Pubmed]
  11. Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation. Harum, K.H., Alemi, L., Johnston, M.V. Neurology (2001) [Pubmed]
  12. B cell IL-7. Human B cell lines constitutively secrete IL-7 and express IL-7 receptors. Benjamin, D., Sharma, V., Knobloch, T.J., Armitage, R.J., Dayton, M.A., Goodwin, R.G. J. Immunol. (1994) [Pubmed]
  13. The influence of concomitant drug therapy on the efficacy of atrial overdrive stimulation for prevention of atrial tachyarrhythmias. Konz, K.H., Danilovic, D., Brachmann, J., Attuel, P., el Allaf, D., John, C., Malinowski, K., Le Blanc, U., Szendey, I., Schibgilla, V., Motzke, T. Pacing and clinical electrophysiology : PACE. (2003) [Pubmed]
  14. Calcium dobesilate (CLS 2210) protects the myocardium in early acute myocardial infarction: a preliminary randomized, double-blind, placebo-controlled study of its effects on biochemical markers. Szlavy, L., Repa, I., Lengyel, I., Lamboy, L. J. Cardiovasc. Pharmacol. (1990) [Pubmed]
  15. RSK2 activity is regulated by its interaction with PEA-15. Vaidyanathan, H., Ramos, J.W. J. Biol. Chem. (2003) [Pubmed]
  16. Cloning and characterization of Xenopus Rsk2, the predominant p90 Rsk isozyme in oocytes and eggs. Bhatt, R.R., Ferrell, J.E. J. Biol. Chem. (2000) [Pubmed]
  17. Effects of bisindolylmaleimide PKC inhibitors on p90RSK activity in vitro and in adult ventricular myocytes. Roberts, N.A., Haworth, R.S., Avkiran, M. Br. J. Pharmacol. (2005) [Pubmed]
  18. Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities. Merienne, K., Pannetier, S., Harel-Bellan, A., Sassone-Corsi, P. Mol. Cell. Biol. (2001) [Pubmed]
  19. Basic fibroblast growth factor inhibits radiation-induced apoptosis of HUVECs. II. The RAS/MAPK pathway and phosphorylation of BAD at serine 112. Gu, Q., Wang, D., Wang, X., Peng, R., Liu, J., Deng, H., Wang, Z., Jiang, T. Radiat. Res. (2004) [Pubmed]
  20. Human rsk isoforms: cloning and characterization of tissue-specific expression. Moller, D.E., Xia, C.H., Tang, W., Zhu, A.X., Jakubowski, M. Am. J. Physiol. (1994) [Pubmed]
  21. Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients. Bjørbaek, C., Vik, T.A., Echwald, S.M., Yang, P.Y., Vestergaard, H., Wang, J.P., Webb, G.C., Richmond, K., Hansen, T., Erikson, R.L. Diabetes (1995) [Pubmed]
  22. Evaluation of the role of protein kinase Czeta in insulin-induced heart 6-phosphofructo-2-kinase activation. Mouton, V., Vertommen, D., Bertrand, L., Hue, L., Rider, M.H. Cell. Signal. (2007) [Pubmed]
  23. p90 ribosomal S6 kinase 2 is associated with and dephosphorylated by protein phosphatase 2Cdelta. Doehn, U., Gammeltoft, S., Shen, S.H., Jensen, C.J. Biochem. J. (2004) [Pubmed]
  24. Rsk2 allosterically activates estrogen receptor alpha by docking to the hormone-binding domain. Clark, D.E., Poteet-Smith, C.E., Smith, J.A., Lannigan, D.A. EMBO J. (2001) [Pubmed]
  25. Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. Tirosh, A., Potashnik, R., Bashan, N., Rudich, A. J. Biol. Chem. (1999) [Pubmed]
  26. Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway. Martin, K.A., Schalm, S.S., Richardson, C., Romanelli, A., Keon, K.L., Blenis, J. J. Biol. Chem. (2001) [Pubmed]
  27. Epidermal growth factor stimulates RSK2 activation through activation of the MEK/ERK pathway and src-dependent tyrosine phosphorylation of RSK2 at Tyr-529. Kang, S., Dong, S., Guo, A., Ruan, H., Lonial, S., Khoury, H.J., Gu, T.L., Chen, J. J. Biol. Chem. (2008) [Pubmed]
  28. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Yntema, H.G., van den Helm, B., Kissing, J., van Duijnhoven, G., Poppelaars, F., Chelly, J., Moraine, C., Fryns, J.P., Hamel, B.C., Heilbronner, H., Pander, H.J., Brunner, H.G., Ropers, H.H., Cremers, F.P., van Bokhoven, H. Genomics (1999) [Pubmed]
  29. Activation of actin-activated MgATPase activity of myosin II by phosphorylation with MAPK-activated protein kinase-1b (RSK-2). Suizu, F., Ueda, K., Iwasaki, T., Murata-Hori, M., Hosoya, H. J. Biochem. (2000) [Pubmed]
  30. Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases. Zhao, Y., Bjorbaek, C., Moller, D.E. J. Biol. Chem. (1996) [Pubmed]
  31. Mutational analysis of ribosomal S6 kinase 2 shows differential regulation of its kinase activity from that of ribosomal S6 kinase 1. Phin, S., Kupferwasser, D., Lam, J., Lee-Fruman, K.K. Biochem. J. (2003) [Pubmed]
  32. The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation. Clark, D.E., Errington, T.M., Smith, J.A., Frierson, H.F., Weber, M.J., Lannigan, D.A. Cancer Res. (2005) [Pubmed]
  33. Ataxia telangiectasia mutated proteins, MAPKs, and RSK2 are involved in the phosphorylation of STAT3. Zhang, Y., Cho, Y.Y., Petersen, B.L., Bode, A.M., Zhu, F., Dong, Z. J. Biol. Chem. (2003) [Pubmed]
  34. Rapid immunoblot and kinase assay tests for a syndromal form of X linked mental retardation: Coffin-Lowry syndrome. Merienne, K., Jacquot, S., Trivier, E., Pannetier, S., Rossi, A., Scott, C., Schinzel, A., Castellan, C., Kress, W., Hanauer, A. J. Med. Genet. (1998) [Pubmed]
  35. Total hip replacement with the CLS expansion shell and a structural femoral head autograft for patients with congenital hip disease. Rozkydal, Z., Janícek, P., Smíd, Z. The Journal of bone and joint surgery. American volume. (2005) [Pubmed]
 
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