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Science 6 August 1999:
Vol. 285. no. 5429, pp. 886 - 891
DOI: 10.1126/science.285.5429.886
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Reports

Requirement of Rsk-2 for Epidermal Growth Factor-Activated Phosphorylation of Histone H3

Paolo Sassone-Corsi, 1*dagger Craig A. Mizzen, 2dagger Peter Cheung, 2 Claudia Crosio, 1 Lucia Monaco, 1 Sylvie Jacquot, 1 André Hanauer, 1 C. David Allis 2*

During the immediate-early response of mammalian cells to mitogens, histone H3 is rapidly and transiently phosphorylated by one or more unidentified kinases. Rsk-2, a member of the pp90rsk family of kinases implicated in growth control, was required for epidermal growth factor (EGF)-stimulated phosphorylation of H3. RSK-2 mutations in humans are linked to Coffin-Lowry syndrome (CLS). Fibroblasts derived from a CLS patient failed to exhibit EGF-stimulated phosphorylation of H3, although H3 was phosphorylated during mitosis. Introduction of the wild-type RSK-2 gene restored EGF-stimulated phosphorylation of H3 in CLS cells. In addition, disruption of the RSK-2 gene by homologous recombination in murine embryonic stem cells abolished EGF-stimulated phosphorylation of H3. H3 appears to be a direct or indirect target of Rsk-2, suggesting that chromatin remodeling might contribute to mitogen-activated protein kinase-regulated gene expression.

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, B. P. 163, 67404 Illkirch-Strasbourg, France.
2 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
*   To whom correspondence should be addressed. E-mail: paolosc{at}igbmc.u-strasbg.fr; allis{at}virginia.edu

dagger    These authors contributed equally to this work. The contributions of the Sassone-Corsi and Allis labs were equal.

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Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions.
G. Pearson, F. Robinson, T. Beers Gibson, B.-e Xu, M. Karandikar, K. Berman, and M. H. Cobb (2001)
Endocr. Rev. 22, 153-183
   Abstract »    Full Text »
Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation.
J. M. Kyriakis and J. Avruch (2001)
Physiol Rev 81, 807-869
   Abstract »    Full Text »    PDF »
Rett syndrome and the MECP2 gene.
T. Webb and F. Latif (2001)
J. Med. Genet. 38, 217-223
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Cognitive impairment in Coffin-Lowry syndrome correlates with reduced RSK2 activation.
K. H. Harum, L. Alemi, and M. V. Johnston (2001)
Neurology 56, 207-214
   Abstract »    Full Text »    PDF »
Differential regulation of CENP-A and histone H3 phosphorylation in G2/M.
S. Zeitlin, C. Barber, C. Allis, and K Sullivan (2001)
J. Cell Sci. 114, 653-661
   Abstract »    PDF »
Altered Extracellular Signal-Regulated Kinase Signaling and Glycogen Metabolism in Skeletal Muscle from p90 Ribosomal S6 Kinase 2 Knockout Mice.
S. D. Dufresne, C. Bjørbæk, K. El-Haschimi, Y. Zhao, W. G. Aschenbach, D. E. Moller, and L. J. Goodyear (2001)
Mol. Cell. Biol. 21, 81-87
   Abstract »    Full Text »
Chromatin modification and disease.
C. A Johnson (2000)
J. Med. Genet. 37, 905-915
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Histone H1 and H3 Dephosphorylation Are Differentially Regulated by Radiation-induced Signal Transduction Pathways.
C. Y. Guo, C. Mizzen, Y. Wang, and J. M. Larner (2000)
Cancer Res. 60, 5667-5672
   Abstract »    Full Text »
Jil-1, a Chromosomal Kinase Implicated in Regulation of Chromatin Structure, Associates with the Male Specific Lethal (Msl) Dosage Compensation Complex.
Y. Jin, Y. Wang, J. Johansen, and K. M. Johansen (2000)
J. Cell Biol. 149, 1005-1010
   Abstract »    Full Text »    PDF »
Ribosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c-Fos gene.
J. C. Bruning, J. A. Gillette, Y. Zhao, C. Bjorbaeck, J. Kotzka, B. Knebel, H. Avci, B. Hanstein, P. Lingohr, D. E. Moller, et al. (2000)
PNAS 97, 2462-2467
   Abstract »    Full Text »    PDF »
CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair.
P Ridgway and G Almouzni (2000)
J. Cell Sci. 113, 2647-2658
   Abstract »    PDF »
Histone H2B Phosphorylation in Mammalian Apoptotic Cells. AN ASSOCIATION WITH DNA FRAGMENTATION.
K. Ajiro (2000)
J. Biol. Chem. 275, 439-443
   Abstract »    Full Text »    PDF »
Chromatin-association of the Polycomb group protein BMI1 is cell cycle-regulated and correlates with its phosphorylation status.
J. Voncken, D Schweizer, L Aagaard, L Sattler, M. Jantsch, and M van Lohuizen (1999)
J. Cell Sci. 112, 4627-4639
   Abstract »    PDF »
Control Sites of Ribosomal S6 Kinase B and Persistent Activation through Tumor Necrosis Factor.
M. Tomas-Zuber, J.-L. Mary, and W. Lesslauer (2000)
J. Biol. Chem. 275, 23549-23558
   Abstract »    Full Text »    PDF »
C-terminal Elements Control Location, Activation Threshold, and p38 Docking of Ribosomal S6 Kinase B (RSKB).
M. Tomas-Zuber, J.-L. Mary, F. Lamour, D. Bur, and W. Lesslauer (2001)
J. Biol. Chem. 276, 5892-5899
   Abstract »    Full Text »    PDF »


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