The protein kinase Pelle mediates feedback regulation in the Drosophila Toll signaling pathway.
Dorsoventral polarity in the Drosophila embryo is established through a signal transduction cascade triggered in ventral and ventrolateral regions. Activation of a transmembrane receptor, Toll, leads to localized recruitment of the adaptor protein Tube and protein kinase Pelle. Signaling through these components directs degradation of the IkappaB-like inhibitor Cactus and nuclear translocation of the Rel protein Dorsal. Here we show through confocal immunofluorescence microscopy that Pelle functions to downregulate the signal-dependent relocalization of Tube. Inactivation of the Pelle kinase domain, or elimination of the Tube-Pelle interaction, dramatically increases Tube recruitment to the ventral plasma membrane in regions of active signaling. We also characterize a large collection of pelle alleles, identifying the molecular lesions in these alleles and their effects on Pelle autophosphorylation, Tube phosphorylation and Tube relocalization. Our results point to a mechanism operating to modulate the domain or duration of signaling downstream from Tube and Pelle.
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Section of Cell and Developmental Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0634, USA.
Bergmann
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Wasserman
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D005246:Feedback; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008322:Mammals; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C084727:tub protein, Drosophila; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases