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Mol. Cell. Biol. 22 (6): 1792-1803

Copyright © 2002 by the American Society for Microbiology. All rights reserved.

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

Hua-Wei Chen,1 Maria Julia Marinissen,2 Su-Wan Oh,1 Xiu Chen,1 Michael Melnick,3 Norbert Perrimon,4 J. Silvio Gutkind,2 and Steven X. Hou1*

The Laboratory of Immunobiology, National Institutes of Health, National Cancer Institute at Frederick, Frederick, Maryland 21702,1 Laboratory of Cell Signaling, New England BioLabs, Beverly, Massachusetts 01915,3 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892,2 Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 021154

Received for publication 31 July 2001. Revision received 18 September 2001. Accepted for publication 4 December 2001.

Abstract: 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.

* Corresponding author. Mailing address: Building 560, Room 12-70, NCI-FCRDC, National Cancer Institute at Frederick, Frederick, MD 21702. Phone: (301) 846-1589. Fax: (301) 846-6145. E-mail: shou{at}mail.ncifcrf.gov.

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