title: Association between a transmembrane protein tyrosine phosphatase and the cadherin-catenin complex.
abstract: Cadherins are calcium-dependent cell adhesion molecules that play fundamental roles in embryonic development, tissue morphogenesis, and cancer. A prerequisite for their function is association with the actin cytoskeleton via the catenins. Tyrosine phosphorylation of beta-catenin, which correlates with a reduction in cadherin-dependent cell adhesion, may provide cells with a mechanism to regulate cadherin activity. Here we report that beta-catenin immune precipitates from PC12 cells contain tyrosine phosphatase activity which dephosphorylates beta-catenin in vitro. In addition, we show that a member of the leukocyte antigen-related protein (LAR)-related transmembrane tyrosine phosphatase family (LAR-PTP) associates with the cadherin-catenin complex. This association required the amino-terminal domain of beta-catenin but does not require the armadillo repeats, which mediate association with cadherins. The interaction also is detected in PC9 cells, which lack alpha-catenin. Thus, the association is not mediated by alpha-catenin or by cadherins. Interestingly, LAR-PTPs are phosphorylated on tyrosine in a TrkA-dependent manner, and their association with the cadherin-catenin complex is reduced in cells treated with NGF. We propose that changes in tyrosine phosphorylation of beta-catenin mediated by TrkA and LAR-PTPs control cadherin adhesive function during processes such as neurite outgrowth.
authors.affiliation: Department of Physiology, University of California, San Francisco 94143-0724, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Kypta
authors.forename: H
authors.initials: H
authors.lastname: Su
authors.forename: L F
authors.initials: LF
authors.lastname: Reichardt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells / Q000737:chemistry / Q000201:enzymology; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000737:chemistry; D007136:Immunoglobulins / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells / Q000737:chemistry / Q000201:enzymology; D010766:Phosphorylation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D007136:Immunoglobulins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D020917:Receptor, trkA; D017027:Protein Tyrosine Phosphatases