MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts.
Journal:
Mol. Cell. Biol. 2002 AprAuthors:
Wiggin GR, Soloaga A, Foster JM, Murray-Tait V, Cohen P, Arthur JS
Abstract
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 transcript
...[more]ion 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.[less]
Mesh Headings:
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