RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE PTP-MU ASSOCIATES WITH CADHERINS AND CATENINS IN-VIVO

The extracellular segment of the receptor-type protein tyrosine phosph atase PTP mu, possesses an MAM domain, an immunoglobulin domain, and f our fibronectin type-III repeats. It binds homophilically, i.e., PTP m u on the surface of one cell binds to PTP mu on an apposing cell, and the binding site lies within the immunoglobulin domain. The intracellu lar segment of PTP mu has two PTP domains and a juxtamembrane segment that is homologous to the conserved intracellular domain of the cadher ins. In cadherins, this segment interacts with proteins termed catenin s to mediate association with the actin cytoskeleton. In this article, we demonstrate that PTP mu associates with a complex containing cadhe rins, alpha- and beta-catenin in mink lung (MvLu) cells, and in rat he art, lung, and brain tissues. Greater than 80% of the cadherin in the cell is cleared from Triton X-100 lysates of MvLu cells after immuno-p recipitation with antibodies to PTP mu; however, the complex is dissoc iated when lysates are prepared in more stringent, SDS-containing RIPA buffer. In vitro binding studies demonstrated that the intracellular segment of PTP mu binds directly to the intracellular domain of E-cadh erin, but not to alpha- or beta-catenin. Consistent with their ability to interact in vivo, PTP mu, cadherins, and catenins all localized to points of cell-cell contact in MvLu cells, as assessed by immunocytoc hemical staining. After pervanadate treatment of MvLu cells, which inh ibits cellular tyrosine phosphatase activity including PTP mu, the cad herins associated with PTP mu are now found in a tyrosine-phosphorylat ed form, indicating that the cadherins may be an endogenous substrate for PTP mu. These data suggest that PTP mu may be one of the enzymes t hat regulates the dynamic tyrosine phosphorylation, and thus function, of the cadherin/catenin complex in vivo.