Drosophila Armadillo and its vertebrate homolog beta-catenin play esse
ntial roles both in the transduction of Wingless/Wnt cell-cell signals
and in the function of cell-cell adherens junctions, Wingless and Wnt
s direct numerous cell fate choices during development, We generated a
mutant protein, Armadillo(S10), with a 54 amino acid deletion in its
N-terminal domain. This mutant is constitutively active in Wingless si
gnaling; its activity is independent of both Wingless signal and endog
enous wild-type Armadillo. Armadillo's role in signal transduction is
normally negatively regulated by Zeste-white 3 kinase, which modulates
Armadillo protein stability. Armadillo(S10) is more stable than wild-
type Armadillo, suggesting that it is less rapidly targeted for degrad
ation. We show that Armadillo(S10) has escaped from negative regulatio
n by Zeste white-3 kinase, and thus accumulates outside junctions even
in the absence of Wingless signal, Finally, we present data implicati
ng kinases in addition to Zeste white-3 in Armadillo phosphorylation,
We discuss two models for the negative regulation of Armadillo in norm
al development and discuss how escape from this regulation contributes
to tumorigenesis.