MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells

被引:159
作者
Arthur, JSC [1 ]
Cohen, P [1 ]
机构
[1] Univ Dundee, Dept Biochem, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland
基金
英国医学研究理事会;
关键词
cyclic AMP-responsive element binding protein; phosphorylation; mitogen- and stress-activated protein kinase 1 MAP kinase-activated protein kinase 1;
D O I
10.1016/S0014-5793(00)02031-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:44 / 48
页数:5
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