THE ELK-1 ETS-DOMAIN TRANSCRIPTION FACTOR CONTAINS A MITOGEN-ACTIVATED PROTEIN-KINASE TARGETING MOTIF

The phosphorylation of transcription factors by mitogen-activated prot ein kinases (MAP) is a pivotal event in the cellular response to the a ctivation of MAP kinase signal transduction pathways. Mitogenic and st ress stimuli activate different pathways and lead to the activation of distinct groups of target proteins. Elk-l is targeted by three distin ct MAP kinase pathways. In this study, we demonstrate that the MAP kin ase ERK2 is targeted to Elk-l by a domain which is distinct from, and located N-terminally to, its phosphoacceptor motifs. Targeting via thi s domain is essential for the efficient and rapid phosphorylation of E lk-l in vitro and full and rapid activation in vivo. Specific residues involved in ERK targeting have been identified. Our data indicate tha t the targeting of different classes of MAP kinases to their nuclear s ubstrates may be a common mechanism to increase the specificity and ef ficiency of this signal transduction pathway.