Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3.
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.
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, B. P. 163, 67404 Illkirch-Strasbourg, France. paolosc@igbmc.u-strasbg.fr
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Cheung
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Monaco
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D016475:3T3 Cells; D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013577:Syndrome
D006657:Histones; D004815:Epidermal Growth Factor; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases