CKA, a Novel Multidomain Protein, Regulates the JUN N-Terminal Kinase Signal Transduction Pathway in Drosophila

The Drosophila melanogaster JUN N-terminal kinase (DJNK) and DPP (decapentaplegic) signal transduction pathways coordinately regulate epithelial cell sheet movement during the process of dorsal closure in the embryo. By a genetic screen of mutations affecting dorsal closure in Drosophila, we have now identified a multidomain protein, connector of kinase to AP-1 (cka), that functions in the DJNK pathway and controls the localized expression of dpp in the leading-edge cells. We have also investigated how CKA acts. This unique molecule forms a complex with HEP (DJNKK), BSK (DJNK), DJUN, and DFOS. Complex formation activates BSK kinase, which in turn phosphorylates and activates DJUN and DFOS. These data suggest that CKA represents a novel molecule regulating AP-1 activity by organizing a molecular complex of kinases and transcription factors, thus coordinating the spatial-temporal expression of AP-1-regulated genes. Morphogenetic movements play a central role in the establishment of the overall body organization and shape during metazoan development. Most types of morphogenetic movements involve epithelial cell invagination and spreading (epiboly). In Drosophila melanogaster, the morphogenetic movement that occurs during dorsal closure (DC) of the embryonic epidermis has provided an excellent system for characterizing the molecular mechanisms underlying the coordinated movements of epithelial cell layers (8, 13, 25, 26, 38). DC is a major morphogenetic event that occurs during midembryogenesis. DC relies predominately on cell shape changes within the postmitotic epidermis. These changes are initiated in two symmetric dorsalmost rows of epidermal cells, known as the leading-edge (LE) cells, followed by the stretching of the more lateral epidermal cells, and are finished with the fusion of the two rows of LE cells at the dorsal midline (4, 23, 43). Embryos that fail to complete DC due to mutations in the genes required for this process die with a characteristic dorsalopen phenotype (14, 27, 29, 41). Based on molecular data, two