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Molecular and Cellular Biology, April 2002, p. 2871-2881, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2871-2881.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

MSK1 and MSK2 Are Required for the Mitogen- and Stress-Induced Phosphorylation of CREB and ATF1 in Fibroblasts

Giselle R. Wiggin, Ana Soloaga, Julia M. Foster, Victoria Murray-Tait, Philip Cohen, and J. Simon C. Arthur*

MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland

Received 17 October 2001/ Returned for modification 20 November 2001/ Accepted 7 January 2002

Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.

* Corresponding author. Mailing address: MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow St., Dundee DD1 5EH, Scotland. Phone: 44 1382 344726. Fax: 44 1382 223778. E-mail: J.S.C.ARTHUR{at}dundee.ac.uk.

Molecular and Cellular Biology, April 2002, p. 2871-2881, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2871-2881.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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