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Balsamo, J, Arregui, C, Leung, T and Lilien, J (1998) The nonreceptor protein tyrosine phosphatase PTP1B binds to the cytoplasmic domain of N-cadherin and regulates the cadherin-actin linkage. J. Cell Biol. 143:523-32

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 beta- or gamma- catenin. Phosphorylation of beta-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 beta-catenin, thus maintaining the cadherin-actin connection (). 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 beta-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.

PubMed PMC2132848

Actins/metabolism; Animals; Cadherins/metabolism; Catalytic Domain; Cell Adhesion/physiology; Cell Fractionation; Cell Line; Chick Embryo; Cloning, Molecular; Cytoskeletal Proteins/metabolism; Cytoskeleton/metabolism; DNA, Complementary/genetics; DNA, Complementary/isolation & purification; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Molecular Sequence Data; Phosphorylation; Protein Tyrosine Phosphatases/chemistry; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/metabolism; Retina/cytology; Retina/enzymology; Sequence Homology, Amino Acid; Trans-Activators; Transfection; Tyrosine/metabolism; beta Catenin