Wiggin Giselle R, Soloaga Ana, Foster Julia M, Murray-Tait Victoria, Cohen Philip, Arthur J Simon C
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Mol Cell Biol. 2002 Apr;22(8):2871-81. doi: 10.1128/MCB.22.8.2871-2881.2002.
Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.
利用丝裂原和应激激活蛋白激酶1（MSK1）和MSK2的小鼠基因敲除模型以及MSK1和MSK2的双基因敲除模型，我们发现这些蛋白激酶是原代胚胎成纤维细胞中应激诱导的转录因子CREB和ATF1磷酸化所必需的。相比之下，丝裂原诱导的CREB和ATF1磷酸化显著降低，但并未完全消除。丝裂原和应激诱导的CREB在Ser133位点的磷酸化与包括c-fos、junB和egr1在内的多个 immediate early基因的转录有关。MSK1和MSK2双基因敲除导致成纤维细胞中对茴香霉素或UV-C辐射的反应中c-fos和junB基因转录减少50%，但对十四烷酰佛波醇乙酸酯或表皮生长因子的反应中仅略有减少。在MSK1/MSK2双基因敲除中，egr1对丝裂原和应激刺激的转录以及应激诱导的细胞凋亡均未受影响。
