This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Siomi, M. C.
Right arrow Articles by Siomi, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Siomi, M. C.
Right arrow Articles by Siomi, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2002, p. 8438-8447, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8438-8447.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Casein Kinase II Phosphorylates the Fragile X Mental Retardation Protein and Modulates Its Biological Properties

Mikiko C. Siomi,* Kyoko Higashijima, Akira Ishizuka, and Haruhiko Siomi

Institute for Genome Research, University of Tokushima, Kuramoto, Tokushima 770-8503, Japan

Received 28 May 2002/ Returned for modification 12 August 2002/ Accepted 6 September 2002

Fragile X syndrome is caused by loss of FMR1 protein expression. FMR1 binds RNA and associates with polysomes in the cytoplasm; thus, it has been proposed to function as a regulator of gene expression at the posttranscriptional level. Posttranslational modification of FMR1 had previously been suggested to regulate its activity, but no experimental support for this model has been reported to date. Here we report that FMR1 in Drosophila melanogaster (dFMR1) is phosphorylated in vivo and that the homomer formation and the RNA-binding activities of dFMR1 are modulated by phosphorylation in vitro. Identification of a protein phosphorylating dFMR1 showed it to be Drosophila casein kinase II (dCKII). dCKII directly interacts with and phosphorylates dFMR1 in vitro. The phosphorylation site in dFMR1 was identified as Ser406, which is highly conserved among FMR1 family members from several species. Using mass spectrometry, we established that Ser406 of dFMR1 is indeed phosphorylated in vivo. Furthermore, human FMR1 (hFMR1) is also phosphorylated in vivo, and alteration of the conserved Ser500 in hFMR1 abolishes phosphorylation by CKII in vitro. These studies support the model that the biological functions of FMR1, such as regulation of gene expression, are likely regulated by its phosphorylation.

* Corresponding author. Mailing address: Institute for Genome Research, University of Tokushima, Kuramoto, Tokushima 770-8503, Japan. Phone: 81-88-633-9456. Fax: 81-88-633-9451. E-mail: siomim{at}genome.tokushima-u.ac.jp.

Molecular and Cellular Biology, December 2002, p. 8438-8447, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8438-8447.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cziko, A.-M. J., McCann, C. T., Howlett, I. C., Barbee, S. A., Duncan, R. P., Luedemann, R., Zarnescu, D., Zinsmaier, K. E., Parker, R. R., Ramaswami, M. (2009). Genetic Modifiers of dFMR1 Encode RNA Granule Components in Drosophila. Genetics 182: 1051-1060 [Abstract] [Full Text]  
  • Didiot, M.-C., Tian, Z., Schaeffer, C., Subramanian, M., Mandel, J.-L., Moine, H. (2008). The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer. Nucleic Acids Res 36: 4902-4912 [Abstract] [Full Text]  
  • Narayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G. J., Warren, S. T. (2008). S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade. J. Biol. Chem. 283: 18478-18482 [Abstract] [Full Text]  
  • Piazzon, N., Rage, F., Schlotter, F., Moine, H., Branlant, C., Massenet, S. (2008). In Vitro and in Cellulo Evidences for Association of the Survival of Motor Neuron Complex with the Fragile X Mental Retardation Protein. J. Biol. Chem. 283: 5598-5610 [Abstract] [Full Text]  
  • Pfeiffer, B. E., Huber, K. M. (2007). Fragile X Mental Retardation Protein Induces Synapse Loss through Acute Postsynaptic Translational Regulation. J. Neurosci. 27: 3120-3130 [Abstract] [Full Text]  
  • Davidovic, L., Bechara, E., Gravel, M., Jaglin, X. H., Tremblay, S., Sik, A., Bardoni, B., Khandjian, E. W. (2006). The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons. Hum Mol Genet 15: 1525-1538 [Abstract] [Full Text]  
  • Stetler, A., Winograd, C., Sayegh, J., Cheever, A., Patton, E., Zhang, X., Clarke, S., Ceman, S. (2006). Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp. Hum Mol Genet 15: 87-96 [Abstract] [Full Text]  
  • Mattick, J. S., Makunin, I. V. (2005). Small regulatory RNAs in mammals. Hum Mol Genet 14: R121-R132 [Abstract] [Full Text]  
  • Zhang, Y. Q., Friedman, D. B., Wang, Z., Woodruff, E. III, Pan, L., O'Donnell, J., Broadie, K. (2005). Protein Expression Profiling of the Drosophila Fragile X Mutant Brain Reveals Up-regulation of Monoamine Synthesis. Mol. Cell. Proteomics 4: 278-290 [Abstract] [Full Text]  
  • Garnon, J., Lachance, C., Di Marco, S., Hel, Z., Marion, D., Ruiz, M. C., Newkirk, M. M., Khandjian, E. W., Radzioch, D. (2005). Fragile X-related Protein FXR1P Regulates Proinflammatory Cytokine Tumor Necrosis Factor Expression at the Post-transcriptional Level. J. Biol. Chem. 280: 5750-5763 [Abstract] [Full Text]  
  • Michel, C. I., Kraft, R., Restifo, L. L. (2004). Defective Neuronal Development in the Mushroom Bodies of Drosophila Fragile X Mental Retardation 1 Mutants. J. Neurosci. 24: 5798-5809 [Abstract] [Full Text]  
  • Ceman, S., O'Donnell, W. T., Reed, M., Patton, S., Pohl, J., Warren, S. T. (2003). Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet 12: 3295-3305 [Abstract] [Full Text]  
  • Mazroui, R., Huot, M.-E., Tremblay, S., Boilard, N., Labelle, Y., Khandjian, E. W. (2003). Fragile X Mental Retardation protein determinants required for its association with polyribosomal mRNPs. Hum Mol Genet 12: 3087-3096 [Abstract] [Full Text]  
  • Bardoni, B., Castets, M., Huot, M.-E., Schenck, A., Adinolfi, S., Corbin, F., Pastore, A., Khandjian, E. W., Mandel, J.-L. (2003). 82-FIP, a novel FMRP (Fragile X Mental Retardation Protein) interacting protein, shows a cell cycle-dependent intracellular localization. Hum Mol Genet 12: 1689-1698 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»