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.
Mesh Terms:
3T3 Cells, Abnormalities, Multiple, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Transformed, Cell Nucleus, Cells, Cultured, Epidermal Growth Factor, Gene Expression Regulation, Gene Targeting, Histones, Humans, Mice, Mitosis, Mutation, Phosphorylation, Ribosomal Protein S6 Kinases, Signal Transduction, Stem Cells, Syndrome
Science
Date: Aug. 06, 1999
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