CKA Acts as Scaffold for AP-1 Activation

Abstract

Mutations in genes involved in the Drosophila c-Jun NH 2 -terminal kinase [(DJNK), also called Basket (BSK)] pathway lead to the fatal dorsal-open phenotype, which is characterized by the inability of rows of dorsal epidermal cells to fuse at the dorsal midline. Chen et al . report the cloning and characterization of a gene, connector of kinase to AP-1 ( cka ), that functions in this signaling pathway. Mutations in the cka gene blocked dorsal closure in Drosophila embryos. Overexpressed CKA associated with the transcription factors DFOS and DJUN (constituents of the transcription factor AP-1), and the protein kinases HEP [hemipterous, a JNK kinase (JNKK)] and BSK, suggesting that CKA acts as an intracellular scaffold molecule, bringing together several signaling molecules for more efficient transduction. However, in the presence of overexpressed HEP and BSK, CKA appeared to bind only HEP, and the molecular size of HEP seemed to increase. The authors speculate that HEP might bind to and phosphorylate CKA and BSK in the complex, but that phosphorylation of CKA might change its conformation, allowing activated BSK to leave the complex. The presence of CKA enhanced BSK's ability to phosphorylate substrates including DFOS and DJUN. Thus, CKA appears to participate in organizing protein kinases and transcription factors involved in AP-1-mediated gene expression. H.-W. Chen, M. J. Marinissen, S.-W. Oh, X. Chen, M. Melnick, N. Perrimon, J. S. Gutkind, S. X. Hou, CKA, a novel multidomain protein, regulates the JUN N-terminal kinase signal transduction pathway in Drosophila . Mol. Cell. Biol. 22 , 1792-1803 (2002). [Abstract] [Full Text]