MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells
MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells
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DOI：
10.1016/s0014-5793(00)02031-7
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发表时间：
2000-09-29
期刊：
影响因子：
3.5
通讯作者：
Cohen, P
中科院分区：
文献类型：
--
作者：
Arthur, JSC;Cohen, P
小鼠胚胎干（ES）细胞的MSK 1基因的破坏纯合子没有检测到MSK 1的活性。然而，它们的激活剂（细胞外信号相关激酶（ERK）1/ERK 2）在有丝分裂原和应激活化蛋白激酶（MSK）1-/-和野生型细胞中响应于十四烷酰佛波醇乙酸酯（TPA）和表皮生长因子（EGF）而被正常刺激，TPA和EGF诱导c1环AMP反应元件结合蛋白（CREB）在Ser-113和ATF 1在Ser-113的磷酸化。63，并且这通过抑制促分裂原活化蛋白激酶级联而被消除。相反，TPA和EGF诱导的CREB/ATF 1磷酸化在MSK-/-细胞中几乎检测不到。然而，基础和毛喉素诱导的磷酸化是相似的，这表明MSK 1“敲除”并不能阻止CREB被环AMP依赖性蛋白激酶磷酸化，因此，在ES细胞促有丝分裂刺激后，MSK 1是CREB和ATF 1磷酸化所必需的。(C)2000年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
Mouse embryonic stem (ES) cells homozygous for disruption of the MSK1 gene had no detectable MSK1 activity. However, their activators (extracellular signal related kinase (ERK)1/ERK2) were stimulated normally in mitogen- and stress-activated protein kinase (MSK)1-/- and wild type cells in response to tetradecanoylphorbol acetate (TPA) and epidermal growth factor (EGF), TPA and EGF induced the phosphorylation of cl cyclic AMP-responsive element binding protein (CREB) at Ser-113 and ATF1 at Ser-63 in wild type cells and this was abolished by inhibition of the mitogen-activated protein kinase cascade. In contrast, the TPA- and EGF-induced phosphorylation of CREB/ATF1 was barely, detectable in MSK-/- cells. However, basal and forskolin-induced phosphorylation was similar, indicating that the MSK1 'knockout' did not prevent CREB phosphorylation by cyclic AMP-dependent protein kinase, Thus MSK1 is required for CREB and ATF1 phosphorylation after mitogenic stimulation of ES cells. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.