Association of Human Protein-tyrosine Phosphatase κ with Members of the Armadillo Family

We have identified a human receptor-like protein-tyrosine phosphatase (PTP) in the mammary carcinoma cell line SK-BR-3, which represents the human homolog of murine PTP kappa (Jiang, Y.-P., Wang, H., D'Eustachio, P., Musacchio, J. M., Schlessinger, J., and Sap, J. (1993) Mot. Cell, Biol, 13, 2942-2951) and was therefore termed hPTP kappa. We show here that hPTP kappa expression is dependent on cell density and find it colocalized with two members of the arm family of proteins, beta-catenin and gamma-catenin/plakoglobin, at adherens junctions, Using both in vitro and in vivo binding assays, we demonstrate specific complex formation between endogenous hPTP kappa and beta- and gamma-catenin/plakoglobin. In addition, we present evidence that suggests that beta-catenin may represent a substrate for the catalytic activity of hPTP kappa, The identification of specific binding partners for this receptor-like PTP provides insight into the mechanisms of its biological action and suggests a role for hPTP kappa in the regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis.