The mechanism of phosphorylation-inducible activation of the ETS-domain transcription factor Elk-1

Protein phosphorylation represents one of the major mechanisms for transcri ption factor activation. Here we demonstrate a molecular mechanism by which phosphorylation by mitogen-activated protein (MAP) kinases leads to change s in transcription factor activity. MAP kinases stimulate DNA binding and t ranscriptional activation mediated by the mammalian ETS-domain transcriptio n factor Elk-1. Phosphorylation of the C-terminal transcriptional activatio n domain induces a conformational change in Elk-1, which accompanies the st imulation of DNA binding. C-terminal phosphorylation is coupled to activati on Of DNA binding by the N-terminal DNA-binding domain via an additional in termediary domain. Activation of DNA binding is mediated by an allosteric m echanism involving the key phosphoacceptor residues. Together, these result s provide a molecular model for how phosphorylation induces changes in Elk- 1 activity.