Abelson Kinase is Critical for Junctional Localization, Stabilization, and Phosphorylation of Armadillo. T.L. Jesse , E.E. Grevengoed , M.A. Peifer. Lineberger Comprehensive Cancer Center and Department of Biology, UNC-Chapel Hill, Chapel Hill, NC.

   Adherens junctions are large multiprotein complexes that mediate cell-cell adhesion and are critical for tissue organization and morphogenesis. The adhesive function of adherens junctions is dependent on cadherins. In epithelial cells, Drosophila Armadillo (Arm), the homologue of vertebrate b-catenin, is a key component of adherens junctions that mediates linkage of the cadherins to the actin cytoskeleton. Arm is critical for cell-cell adhesion during development, and studies in our lab indicate that Arm interacts genetically with the non-receptor tyrosine kinase Abelson (Abl) and its substrate, Enabled, during cell-cell adhesion of epithelial cells. To define the roles of Abl in epithelial tissues and its interactions with Arm during cellular adhesion, we are analyzing Drosophila embryos lacking maternal and zygotic abl. abl mutant embryos die with defects in morphogenetic processes that require cell shape changes and cell migration, including dorsal closure and germband retraction, consistent with a role for Abl during cell-cell adhesion in epithelial cells. We have found that removal of Abl leads to substantial reductions in the accumulation of Arm protein. Reduction in Abl function also leads to reduction of a-catenin levels while levels of DE-cadherin and markers of cell polarity or cytoskeleton are not affected. This suggests that Abl function is critical for stabilization of Arm and a-catenin within adherens junctions. We hypothesize that destabilization of these proteins in the absence of Abl may be the result of their dissociation from adherens junctions in mutant embryos. We also have evidence to suggest that mutations in abl affect phosphorylation levels of Arm, which may regulate the association of Arm within adherens junctions. In addition, characterization of flies expressing an oncogenic form of Abl, Bcr-Abl, is underway.