Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3
Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3
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DOI：
10.1126/science.285.5429.886
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发表时间：
1999-08-06
期刊：
影响因子：
56.9
通讯作者：
Allis, CD
中科院分区：
文献类型：
--
作者：
Sassone-Corsi, P;Mizzen, CA;Allis, CD
在哺乳动物细胞对有丝分裂原的即刻早期反应期间，组蛋白H3被一种或多种未鉴定的激酶快速且瞬时地磷酸化。Rsk-2是参与生长控制的pp 90（rsk）激酶家族的成员，是表皮生长因子（EGF）刺激的H3磷酸化所必需的。人类RSK-2突变与Coffin-Lowry综合征（CLS）有关。来自CLS患者的成纤维细胞未能表现出EGF刺激的H3磷酸化，尽管H3在有丝分裂过程中被磷酸化。野生型RSK-2基因的引入恢复了CLS细胞中EGF刺激的H3磷酸化。此外，在小鼠胚胎干细胞中通过同源重组破坏RSK-2基因，可消除EGF刺激的H3磷酸化。H3似乎是Rsk-2的直接或间接靶点，这表明染色质重塑可能有助于有丝分裂原活化蛋白激酶调节的基因表达。
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 pp90(rsk) 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.