MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14.
Cells respond to mitogenic or stress stimuli by the rapid induction of immediate-early (IE) genes, which occurs concomitantly with the phosphorylation of histone H3 and the high-mobility-group protein HMG-14. In mammalian cells this response is mediated via ERK and p38 MAP kinase pathways, but the identity of the downstream kinase that phosphorylates histone H3 has been contentious. One study, based on Coffin- Lowry cells defective in RSK2, reported that RSK2 was the histone H3 kinase, while a second study, based on the efficiency of RSKs and MSKs as in vitro histone H3 kinases, and their relative susceptibility to kinase inhibitors, suggested that MSKs were responsible. We show here that the histone H3 phosphorylation response is normal in Coffin-Lowry cells. Further more, we show that histone H3 and HMG-14 phosphorylation is severely reduced or abolished in mice lacking MSK1 and MSK2. We also show that, despite this, histone H3 acetylation is unimpaired in these cells and that IE genes can be induced, although at a reduced efficiency. We conclude that MSKs are the major kinases for histone H3 and HMG-14 in response to mitogenic and stress stimuli in fibroblasts.
Soloaga
Ana
A
MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Thomson
Stuart
S
Wiggin
Giselle R
GR
Rampersaud
Navita
N
Dyson
Mark H
MH
Hazzalin
Catherine A
CA
Mahadevan
Louis C
LC
Arthur
J Simon C
JS
D000107:Acetylation; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002478:Cells, Cultured; D016762:Genes, fos; D016758:Genes, jun; D024241:HMGN1 Protein / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D008938:Mitosis; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D024241:HMGN1 Protein; D006657:Histones; D008934:Mitogens; D009707:Nucleosomes; D000841:Anisomycin; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse; C116919:mitogen and stress-activated protein kinase 1; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D013755:Tetradecanoylphorbol Acetate