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Molecular and Cellular Biology, January 1999, p. 321-329, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activated MEK Stimulates Expression of AP-1 Components Independently of Phosphatidylinositol 3-Kinase (PI3-Kinase) but Requires a PI3-Kinase Signal To Stimulate DNA Synthesis

Iris Treinies, Hugh F. Paterson, Steven Hooper, Rebecca Wilson, and Christopher J. Marshall*

CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratory, Institute of Cancer Research, London, SW3 6JB, United Kingdom

Received 13 May 1998/Returned for modification 29 June 1998/Accepted 15 September 1998

To investigate the contribution that ERK/mitogen-activated protein kinase signalling makes to cell cycle progression and gene expression, we have constructed cell lines to express an inducible version of activated MEK1. Using these cells, we show that activation of MEK leads to the expression of Fra-1 and Fra-2 but not c-Fos. Treatment of Ras-transformed cells with the MEK inhibitor PD098059 blocks expression of Fra-1 and Fra-2, showing that in Ras transformation ERK signalling is responsible for Fra-1 and Fra-2 expression. Activation of MEK1 in growth-arrested cells leads to DNA synthesis; however, ERK activation alone is insufficient because the induction of DNA synthesis is blocked by inhibition of phosphatidylinositol 3-kinase (PI3-kinase). Activation of PI3-kinase is indirect, perhaps through autocrine growth factors, and is required for the induction of cyclin D1.

* Corresponding author. Mailing address: CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratory, Institute of Cancer Research, 237 Fulham Rd., London, SW3 6JB, United Kingdom. Phone: 44 (0)171-352-9772. Fax: 44 (0)171-352-5630. E-mail: chrism{at}icr.ac.uk.

Molecular and Cellular Biology, January 1999, p. 321-329, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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