Receptor Protein-tyrosine Phosphatase RPTPμ Binds to and Dephosphorylates the Catenin p120 ctn

doi:10.1074/jbc.275.15.11264

Receptor Protein-tyrosine Phosphatase RPTPμ Binds to and Dephosphorylates the Catenin p120^ctn*

From the ^‡Division of Cellular Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands and the ^§Department of Cell Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2175

Abstract

RPTPμ is a prototypic receptor-like protein-tyrosine phosphatase (RPTP) that mediates homotypic cell-cell interactions. Intracellularly, RPTPμ consists of a relatively large juxtamembrane region and two phosphatase domains, but little is still known about its substrate(s). Here we show that RPTPμ associates with the catenin p120^ctn, a tyrosine kinase substrate and an interacting partner of cadherins. No interaction is detectable between RPTPμ and β-catenin. Furthermore, we show that tyrosine-phosphorylated p120^ctn is dephosphorylated by RPTPμ both in vitro and in intact cells. Complex formation between RPTPμ and p120^ctn does not require tyrosine phosphorylation of p120^ctn. Mutational analysis reveals that both the juxtamembrane region and the second phosphatase domain of RPTPμ are involved in p120^ctnbinding. The RPTPμ-interacting domain of p120^ctn maps to its unique N terminus, a region distinct from the cadherin-interacting domain. A mutant form of p120^ctn that fails to bind cadherins can still associate with RPTPμ. Our findings indicate that RPTPμ interacts with p120^ctn independently of cadherins, and they suggest that this interaction may serve to control the tyrosine phosphorylation state of p120^ctn at sites of cell-cell contact.

Footnotes

↵* This work was supported by the Dutch Cancer Society.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.
↵¶ To whom correspondence should be addressed. Tel.: 31-20-512-1971; Fax: 31-20-512-1989; E-mail: wmoolen@nki.nl.
↵2 G. C. M. Zondag, unpublished observations.
Abbreviations:

PTK

protein-tyrosine kinase

PTP

protein-tyrosine phosphatase

RPTP

receptor-like protein-tyrosine phosphatase

EGF

epidermal growth factor

GST

glutathione S-transferase

HA

hemagglutinin

PBS

phosphate-buffered saline

RIPA

radioimmune precipitation buffer
- Received June 7, 1999.
- Revision received September 30, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.