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© The Rockefeller University Press, 0021-9525/1998//523 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 523-532

Regular Articles

The Nonreceptor Protein Tyrosine Phosphatase PTP1B Binds to the Cytoplasmic Domain of N-Cadherin and Regulates the Cadherin–Actin Linkage



Janne Balsamo, Carlos Arregui, TinChung Leung, and Jack Lilien

Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202

Cadherin-mediated adhesion depends on the association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated by a group of cytoplasmic proteins: {alpha}-and β- or {gamma}- catenin. Phosphorylation of β-catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine phosphatase, bound to the cytoplasmic domain of N-cadherin, is responsible for removing tyrosine-bound phosphate residues from β-catenin, thus maintaining the cadherin–actin connection (Balsamo et al., 1996). Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship between the function of cadherin-bound PTP1B and cadherin-mediated adhesion, we tested the effect of expressing a catalytically inactive form of PTP1B in L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with actin, and β-catenin shows increased phosphorylation on tyrosine residues when compared with parental cells or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found associated with N-cadherin, and recombinant mutant PTP1B binds to N-cadherin in vitro, indicating that the catalytically inactive form acts as a dominant negative, displacing endogenous PTP1B, and rendering cadherin nonfunctional. Our results demonstrate a role for PTP1B in regulating cadherin-mediated cell adhesion.

Key Words: β-catenin • cadherin • protein tyrosine phosphatase • cell–cell adhesion

Abbreviations used in this paper: GFP, green fluorescent protein; GST, glutathione-S-transferase; HA, hemagglutinin; mut, mutant; ORF, open reading frame; PVDF, polyvinylene difluoride; RT, reverse transcription; TL, Transduction Laboratories; wt, wild-type.

TC. Leung's present address is Department of Developmental Biology, Institute Biology I, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.


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