MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts.
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.
Pubmed ID: 11909979 RIS Download
Activating Transcription Factor 1 | Animals | Apoptosis | Calcium-Calmodulin-Dependent Protein Kinases | Cell Division | Cells, Cultured | Cyclic AMP Response Element-Binding Protein | DNA-Binding Proteins | Enzyme Activation | Fibroblasts | Genes, Immediate-Early | Mice | Mice, Knockout | Mitogen-Activated Protein Kinases | Phosphorylation | Protein-Serine-Threonine Kinases | Ribosomal Protein S6 Kinases, 90-kDa | Transcription Factors | Transcription, Genetic | p38 Mitogen-Activated Protein Kinases