Mae mediates MAP kinase phosphorylation of Ets transcription factors in Drosophila


The evolutionarily conserved Ras/mitogen-activated protein kinase (MAPK) cascade is an integral part of the processes of cell division, differentiation, movement and death. Signals received at the cell surface are relayed into the nucleus, where MAPK phosphorylates and thereby modulates the activities of a subset of transcription factors1,2. Here we report the cloning and characterization of a new component of this signal transduction pathway called Mae (for modulator of the activity of Ets). Mae is a signalling intermediate that directly links the MAPK signalling pathway to its downstream transcription factor targets. Phosphorylation by MAPK of the critical serine residue (Ser 127) of the Drosophila transcription factor Yan depends on Mae, and is mediated by the binding of Yan to Mae through their Pointed domains. This phosphorylation is both necessary and sufficient to abrogate transcriptional repression by Yan. Mae also regulates the activity of the transcriptional activator Pointed-P2 by a similar mechanism. Mae is essential for the normal development and viability of Drosophila, and is required in vivo for normal signalling of the epidermal growth factor receptor. Our study indicates that MAPK signalling specificity may depend on proteins that couple specific substrates to the kinase.

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Figure 1: mae sequence and gene organization.
Figure 2: The physical association of Yan and Mae is mediated by their Pnt domains, and this inhibits Yan from binding to DNA.
Figure 3: Mae allows Erk kinase to phosphorylate critical serine or threonine residues of Yan and Pnt-P2, and thus regulates Ets transcriptional activity.
Figure 4: Evidence that mae regulates EGFR signalling in the Drosophila embryonic neurectoderm.

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Data deposits

The sequence has been deposited in GenBank under accession number AF358670.


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We thank S. Bullock, R. Winston, H. McNeill, P. Verrijzer, C. Hill, A. Maata, P. Mason, J. White, J. Brossens, M. Freeman, G. Rubin, T. Laverty and P. Soccorso for advice, discussions and gifts of materials. This work was supported by the Imperial Cancer Research Fund and BBSRC.

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Correspondence to David A. Baker.

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Baker, D., Mille-Baker, B., Wainwright, S. et al. Mae mediates MAP kinase phosphorylation of Ets transcription factors in Drosophila. Nature 411, 330–334 (2001).

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