PMID- 10436156 OWN - NLM STAT- MEDLINE DCOM- 19990819 LR - 20190619 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 285 IP - 5429 DP - 1999 Aug 6 TI - Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. PG - 886-91 AB - 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. FAU - Sassone-Corsi, P AU - Sassone-Corsi P AD - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, ULP, B. P. 163, 67404 Illkirch-Strasbourg, France. paolosc@igbmc.u-strasbg.fr FAU - Mizzen, C A AU - Mizzen CA FAU - Cheung, P AU - Cheung P FAU - Crosio, C AU - Crosio C FAU - Monaco, L AU - Monaco L FAU - Jacquot, S AU - Jacquot S FAU - Hanauer, A AU - Hanauer A FAU - Allis, C D AU - Allis CD LA - eng GR - GM40922/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Histones) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - 3T3 Cells MH - Abnormalities, Multiple/genetics/metabolism MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Cell Line, Transformed MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Epidermal Growth Factor/*pharmacology MH - Gene Expression Regulation MH - Gene Targeting MH - Histones/*metabolism MH - Humans MH - Mice MH - Mitosis MH - Mutation MH - Phosphorylation MH - Ribosomal Protein S6 Kinases/genetics/*metabolism MH - Signal Transduction MH - Stem Cells/cytology/metabolism MH - Syndrome EDAT- 1999/08/07 00:00 MHDA- 1999/08/07 00:01 CRDT- 1999/08/07 00:00 PHST- 1999/08/07 00:00 [pubmed] PHST- 1999/08/07 00:01 [medline] PHST- 1999/08/07 00:00 [entrez] AID - 7736 [pii] AID - 10.1126/science.285.5429.886 [doi] PST - ppublish SO - Science. 1999 Aug 6;285(5429):886-91. doi: 10.1126/science.285.5429.886.