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

  1. Miriam Fuchs,
  2. Thomas Müller,
  3. Markus M. Lerch and
  4. Axel Ullrich
  1. From the Department of Molecular Biology, Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82152 Martinsried, Federal Republic of Germany
  1. To whom all correspondence should be addressed. Tel.: 49-89-8578-2513; Fax: 49-89-857-7866.

Abstract

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 PTPκ (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 hPTPκ. We show here that hPTPκ expression is dependent on cell density and find it colocalized with two members of the arm family of proteins, β-catenin and γ-catenin/plakoglobin, at adherens junctions. Using both in vitro and in vivo binding assays, we demonstrate specific complex formation between endogenous hPTPκ and β- and γ-catenin/plakoglobin. In addition, we present evidence that suggests that β-catenin may represent a substrate for the catalytic activity of hPTPκ. 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 hPTPκ in the regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis.

Footnotes

  • * This work was supported by a grant from SUGEN, Inc. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) Z70660[GenBank].

  • 1 The abbreviations used are:

    PTP

    protein-tyrosine phosphatase

    RPTP

    receptor-like PTP

    PCR

    polymerase chain reaction

    CMV

    cytomegalovirus

    FCS

    fetal calf serum

    GST

    glutathione S-transferase

    PAGE

    polyacrylamide gel electrophoresis

    CHAPS

    3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid.

    • Received February 15, 1996.
    • Revision received April 22, 1996.
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