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Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28

Oncogene volume 24, pages 3492–3502 (2005)Cite this article

Abstract

The Ras-mitogen activated protein kinase (Ras-MAPK) pathway plays an integral role in the formation of human malignancies. Stimulation of this pathway results in phosphorylation of histone H3 at serines 10 and 28 and expression of immediate-early genes. Phosphorylated (serine 10) H3, which is also acetylated on lysine 14, is associated with immediate-early genes. In this report, we investigated the relationship between these two H3 phosphorylation events in parental and ras-transformed fibroblasts. Immunoblot analyses of two-dimensional gel patterns demonstrated that all three H3 variants were phosphorylated after stimulation of the Ras-MAPK pathway and during mitosis. Following stimulation of the Ras-MAPK pathway, H3 phosphorylated on serines 10 and 28 was excluded from regions of highly condensed chromatin and was present in increased levels in ras-transformed cells. Although H3 phosphorylated at serine 10 or 28 was dynamically acetylated, H3 phosphorylated at serine 28 had a higher steady state of acetylation than that of H3 phosphorylated at serine 10. When visualized with indirect immunofluorescence, most foci of phosphorylated serine 28 H3 did not co-localize with foci of H3 phosphorylated on serine 10 or phosphoacetylated on serine 10 and lysine 14, suggesting that these two phosphorylation events act separately to promote gene expression.

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Acknowledgements

This research was supported by a grant from the National Cancer Institute of Canada with funds from the Canadian Cancer Society, a Canada Research Chair to JRD, and a KM Hunter/CIHR Doctoral Research Award to KLD.

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  1. Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba, Canada, R3E 0V9

    Katherine L Dunn & James R Davie

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Correspondence to James R Davie.

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Dunn, K., Davie, J. Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28. Oncogene 24, 3492–3502 (2005). https://doi.org/10.1038/sj.onc.1208521

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