DIFFERENTIAL TARGETING OF MAP KINASES TO THE ETS-DOMAIN TRANSCRIPTIONFACTOR ELK-1

The activation of MAP kinase (MAPK) signal transduction pathways resul ts in the phosphorylation of transcription factors by the terminal kin ases in these cascades. Different pathways are activated by mitogenic and stress stimuli, which lead to the activation of distinct groups of target proteins. The ETS-domain transcription factor Elk-1 is a subst rate for three distinct classes of MAPKs. Elk-1 contains a targeting d omain, the D-domain, which is distinct from the phosphoacceptor moths and is required for efficient phosphorylation and activation by the ER K MAPKs. In this study, we demonstrate that members of the JNK subfami ly of MAPKs are also targeted to Elk-1 by this domain. Targeting via t his domain is essential for the efficient and rapid phosphorylation an d activation of Elk-1 both in vitro and in vivo. The ERK and JNK MAPKs use overlapping yet distinct determinants in the D-domain for targeti ng to Elk-1. In contrast, members of the p38 subfamily of MAPKs are no t targeted to Elk-1 via this domain. Our data therefore demonstrate th at different classes of MAPKs exhibit differential requirements for ta rgeting to Elk-1.