Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor

Yutaka Kato, Richard I. Tapping, Shuang Huang, Mark H. Watson, Richard J. Ulevitch, Jiing Dwan Lee

Research output: Contribution to journalArticle

330 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) induces cell proliferation in a variety of cell types by binding to a prototype transmembrane tyrosine kinase receptor. Ligation of this receptor by EGF activates Erk1 and Erk2, members of the mitogen-activated protein (MAP) kinase family, through a Ras-dependent signal transduction pathway. Despite our detailed understanding of these events, the exact mechanism by which EGF causes cells to proliferate is unclear. Big MAP kinase (Bmk1), also known as Erk5, is a member of the MAP kinase family that is activated in cells in response to oxidative stress, hyperosmolarity and treatment with serum. Here we show that EGF is a potent activator of Bmk1. In contrast to Erk1/2, EGF-mediated activation of Bmk1 occurs independently of Ras and requires the MAP-kinase kinase Mek5. Expression of a dominant- negative form of Bmk1 blocks EGF-induced cell proliferation and prevents cells from entering the S phase of the cell cycle. These results demonstrate that Bmk1 is part of a distinct MAP-kinase signalling pathway that is required for EGF-induced cell proliferation and progression through the cell cycle.

Original languageEnglish (US)
Pages (from-to)713-716
Number of pages4
JournalNature
Volume395
Issue number6703
DOIs
StatePublished - Oct 15 1998

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Epidermal Growth Factor
Cell Proliferation
Mitogen-Activated Protein Kinases
Cell Cycle
Mitogen-Activated Protein Kinase Kinases
Receptor Protein-Tyrosine Kinases
S Phase
Epidermal Growth Factor Receptor
Ligation
Signal Transduction
Oxidative Stress
Serum

ASJC Scopus subject areas

  • General

Cite this

Kato, Y., Tapping, R. I., Huang, S., Watson, M. H., Ulevitch, R. J., & Lee, J. D. (1998). Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature, 395(6703), 713-716. https://doi.org/10.1038/27234

Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. / Kato, Yutaka; Tapping, Richard I.; Huang, Shuang; Watson, Mark H.; Ulevitch, Richard J.; Lee, Jiing Dwan.

In: Nature, Vol. 395, No. 6703, 15.10.1998, p. 713-716.

Research output: Contribution to journalArticle

Kato, Y, Tapping, RI, Huang, S, Watson, MH, Ulevitch, RJ & Lee, JD 1998, 'Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor', Nature, vol. 395, no. 6703, pp. 713-716. https://doi.org/10.1038/27234
Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature. 1998 Oct 15;395(6703):713-716. https://doi.org/10.1038/27234
Kato, Yutaka ; Tapping, Richard I. ; Huang, Shuang ; Watson, Mark H. ; Ulevitch, Richard J. ; Lee, Jiing Dwan. / Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. In: Nature. 1998 ; Vol. 395, No. 6703. pp. 713-716.
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