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MSK2 and MSK1 mediate the mitogen‐ and stress‐induced phosphorylation of histone H3 and HMG‐14
Author(s) -
Soloaga Ana,
Thomson Stuart,
Wiggin Giselle R.,
Rampersaud Navita,
Dyson Mark H.,
Hazzalin Catherine A.,
Mahadevan Louis C.,
Arthur J.Simon C.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg273
Subject(s) - histone h3 , biology , histone , phosphorylation , kinase , mitogen activated protein kinase , microbiology and biotechnology , mapk/erk pathway , p38 mitogen activated protein kinases , ribosomal s6 kinase , protein kinase a , acetylation , biochemistry , gene , p70 s6 kinase 1 , protein kinase b
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.