Proteins are identified from human breast tumor cell lines (MDA-MB-231, T-47D and T-47D/Met) that interact specifically with the substrate-trapping mutant form of Density Enhanced Phosphatase-1 (DEP-1). These proteins include the functional component p120 catenin (p120.sup.ctn), the adaptor protein Gab 1, and the HGF/SF receptor Met. The invention relates to isolated complexes comprising DEP-1 polypeptides in specific association with Met, Gab 1, or p120.sup.ctn, identified herein as DEP-1 substrate polypeptides. Screening assays for agents that alter DEP-1 interaction with DEP-1 substrate polypeptides are also disclosed, as are methods for altering biological signals in cells that are transduced via DEP-1 pathways.