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    Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation

    Mylona, Anastasia and Theillet, F.-X. and Foster, C. and Cheng, T.M. and Miralles, F. and Bates, P.A. and Selenko, P. and Treisman, R. (2016) Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation. Science 354 (6309), pp. 233-237. ISSN 0036-8075.

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    Abstract

    Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow. Mutagenesis experiments showed that phosphorylation of fast and intermediate sites promoted Mediator interaction and transcriptional activation, whereas modification of slow sites counteracted both functions, thereby limiting Elk-1 output. Progressive Elk-1 phosphorylation thus ensures a self-limiting response to ERK activation, which occurs independently of antagonizing phosphatase activity.

    Metadata

    Item Type: Article
    Additional Information: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published at the link above.
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 13 Nov 2018 14:58
    Last Modified: 27 Jul 2019 05:36
    URI: http://eprints.bbk.ac.uk/id/eprint/25124

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