Fuchs M, Müller T, Lerch M M, Ullrich A
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82152 Martinsried, Federal Republic of Germany.
J Biol Chem. 1996 Jul 12;271(28):16712-9. doi: 10.1074/jbc.271.28.16712.
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 PTPkappa (Jiang, Y.-P., Wang, H., D'Eustachio, P., Musacchio, J. M., Schlessinger, J., and Sap, J. (1993) Mol. Cell. Biol. 13, 2942-2951) and was therefore termed hPTPkappa. We show here that hPTPkappa 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 hPTPkappa 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 hPTPkappa. 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 hPTPkappa in the regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis.
我们在乳腺癌细胞系SK-BR-3中鉴定出一种人受体样蛋白酪氨酸磷酸酶（PTP），它是小鼠PTPkappa的人类同源物（Jiang, Y.-P., Wang, H., D'Eustachio, P., Musacchio, J. M., Schlessinger, J., and Sap, J. (1993) Mol. Cell. Biol. 13, 2942 - 2951），因此被命名为hPTPkappa。我们在此表明hPTPkappa的表达依赖于细胞密度，并发现它与臂蛋白家族的两个成员β-连环蛋白和γ-连环蛋白/桥粒斑蛋白在黏附连接处共定位。通过体外和体内结合试验，我们证明了内源性hPTPkappa与β-连环蛋白和γ-连环蛋白/桥粒斑蛋白之间形成特异性复合物。此外，我们提供的证据表明β-连环蛋白可能是hPTPkappa催化活性的底物。这种受体样PTP特异性结合伙伴的鉴定为其生物学作用机制提供了深入了解，并提示hPTPkappa在涉及细胞接触和黏附的过程调控中发挥作用，如生长控制、肿瘤侵袭和转移。
