Publication Date:
1999-08-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sassone-Corsi, P -- Mizzen, C A -- Cheung, P -- Crosio, C -- Monaco, L -- Jacquot, S -- Hanauer, A -- Allis, C D -- GM40922/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Aug 6;285(5429):886-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, ULP, B. P. 163, 67404 Illkirch-Strasbourg, France. paolosc@igbmc.u-strasbg.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10436156" target="_blank"〉PubMed〈/a〉
Keywords:
3T3 Cells
;
Abnormalities, Multiple/genetics/metabolism
;
Animals
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Cell Line, Transformed
;
Cell Nucleus/metabolism
;
Cells, Cultured
;
Epidermal Growth Factor/*pharmacology
;
Gene Expression Regulation
;
Gene Targeting
;
Histones/*metabolism
;
Humans
;
Mice
;
Mitosis
;
Mutation
;
Phosphorylation
;
Ribosomal Protein S6 Kinases/genetics/*metabolism
;
Signal Transduction
;
Stem Cells/cytology/metabolism
;
Syndrome
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
