Mae mediates MAP kinase phosphorylation of Ets transcription factors in Drosophila

The evolutionarily conserved Ras/mitogen-activated protein kinase (MAPK) ca scade is an integral part of the processes of cell division, differentiatio n, movement and death. Signals received at the cell surface are relayed int o the nucleus, where MAPK phosphorylates and thereby modulates the activiti es of a subset of transcription factors(1,2). Here we report the cloning an d characterization of a new component of this signal transduction pathway c alled Mae (for modulator of the activity of Ets). Mae is a signalling inter mediate that directly links the MAPK signalling pathway to its downstream t ranscription factor targets. Phosphorylation by MAPK of the critical serine residue (Ser 127) of the Drosophila transcription factor Yan depends on Ma e, and is mediated by the binding of Yan to Mae through their Pointed domai ns. This phosphorylation is both necessary and sufficient to abrogate trans criptional repression by Yan. Mae also regulates the activity of the transc riptional activator Pointed-P2 by a similar mechanism. Mae is essential for the normal development and viability of Drosophila, and is required in viv o for normal signalling of the epidermal growth factor receptor. Our study indicates that MAPK signalling specificity may depend on proteins that coup le specific substrates to the kinase.