The protein kinase Pelle mediates feedback regulation in the Drosophila Toll signaling pathway

• Published in: Development (Cambridge) Vol. 128; no. 23; pp. 4729 - 4736
• Main Authors: Towb, P, Bergmann, A, Wasserman, S A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01.12.2001
• Subjects: Alleles; Amino Acid Sequence; Animals; Body Patterning; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins; Feedback; Genes, Insect; I^KB protein; IB protein; Insect Proteins - genetics; Insect Proteins - metabolism; Mammals; Membrane Glycoproteins - metabolism; Models, Biological; Molecular Sequence Data; Mutation; Pelle protein; Phenotype; Phosphorylation; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Receptors, Cell Surface; Sequence Homology, Amino Acid; Signal Transduction; Toll protein; Toll-Like Receptors; Tube protein
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.128.23.4729

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 IκB-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.