|
 |
|
|
| Subject Categories: Signal Transduction | Chromatin & Transcription |
|
| The EMBO Journal
(2003) 22, 2788–2797, doi:10.1093/emboj/cdg273 |
|
| MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14 |
|
|
| Ana Soloaga1, Stuart Thomson2, Giselle R. Wiggin1, Navita Rampersaud2, Mark H. Dyson2, Catherine A. Hazzalin2, Louis C. Mahadevan2 and J.Simon C. Arthur1 |
|
|
1 MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK 2 Nuclear Signalling Laboratory, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK To whom correspondence should be addressed J.Simon C. Arthur, j.s.c.arthur@dundee.ac.uk Received 14 January 2003; Revised 11 April 2003; Accepted 14 April 2003. |
|
|
|
| Abstract |
|
| 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. |
|
| Keywords: histone H3, HMG-14, MSK, phosphorylation, RSK2 |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
