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.
Chen
Hua-Wei
HW
The Laboratory of Immunobiology, National Institutes of Health, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Marinissen
Maria Julia
MJ
Oh
Su-Wan
SW
Chen
Xiu
X
Melnick
Michael
M
Perrimon
Norbert
N
Gutkind
J Silvio
JS
Hou
Steven X
SX
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D019476:Insect Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D046911:Macromolecular Substances; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C499664:Cka protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D046911:Macromolecular Substances; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C064196:dpp protein, Drosophila; C435749:kay protein, Drosophila; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C117694:Hep protein, Drosophila; D020929:Mitogen-Activated Protein Kinase Kinases