Activation of the JNK pathway during dorsal closure in Drosophila requires the mixed lineage kinase, slipper.
The Jun kinase (JNK) pathway has been characterized for its role in stimulating AP-1 activity and for modulating the balance between cell growth and death during development, inflammation, and cancer. Six families of mammalian kinases acting at the level of JNKKK have emerged as upstream regulators of JNK activity (MLK, LZK, TAK, ASK, MEKK, and TPL); however, the specificity underlying which kinase is utilized for transducing a distinct signal is poorly understood. In Drosophila, JNK signaling plays a central role in dorsal closure, controlling cell fate and cell sheet morphogenesis during embryogenesis. Notably, in the fly genome, there are single homologs of each of the mammalian JNKKK families. Here, we identify mutations in one of those, a mixed lineage kinase, named slipper (slpr), and show that it is required for JNK activation during dorsal closure. Furthermore, our results show that other putative JNKKKs cannot compensate for the loss of slpr function and, thus, may regulate other JNK or MAPK-dependent processes.
Stronach
Beth
B
Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Perrimon
Norbert
N
D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D003001:Cloning, Molecular; D004330:Drosophila / Q000196:embryology* / Q000201:enzymology / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C093290:MAP3K10 protein, human; C433243:MAP3K9 protein, human; C447860:slpr protein, Drosophila; C482569:MAP2K7 protein, human