Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin

The initiation of gene expression in response to Drosophila receptor tyrosi ne kinase signaling requires the nuclear import of the MAP kinase, D-ERK. H owever, the molecular details of D-ERK translocation are largely unknown. I n this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homo log of vertebrate importin 7, and its gene moleskin, DIM-7 exhibits a dynam ic nuclear localization pattern that overlaps the spatial and temporal prof ile of nuclear, activated D-ERK. Co-immunoprecipitation experiments show th at DIM-7 associates with phosphorylated D-ERK in Drosophila S2 cells. Furth ermore, moleskin mutations enhance hypomorphic and suppress hypermorphic D- ERK mutant phenotypes. Deletion or mutation of moleskin dramatically reduce s the nuclear localization of activated D-ERK. Directly linking DIM-7 to it s nuclear import, this defect can be rescued by the expression of wild-type DIM-7. Mutations in the Drosophila Importin beta homolog Ketel, also reduc e the nuclear localization of activated D-ERK. Together, these data indicat e that DIM-7 and Ketel are components of the nuclear import machinery for a ctivated D-ERK.