title: Roles of the C terminus of Armadillo in Wingless signaling in Drosophila.
abstract: Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Cox
authors.forename: L M
authors.initials: LM
authors.lastname: Pai
authors.forename: C
authors.initials: C
authors.lastname: Kirkpatrick
authors.forename: J
authors.initials: J
authors.lastname: Stein
authors.forename: M
authors.initials: M
authors.lastname: Peifer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D005111:Extrachromosomal Inheritance; D005260:Female; D005816:Genetic Complementation Test; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; C074622:wg protein, Drosophila