Receptor protein tyrosine phosphatase PTPμ associates with cadherins and catenins in vivo

Abstract

The extracellular segment of the receptor-type protein tyrosine phosphatase PTPμ, possesses an MAM domain, an immunoglobulin domain, and four fibronectin type-III repeats. It binds homophilically, i.e., PTPμ on the surface of one cell binds to PTPμ on an apposing cell, and the binding site lies within the immunoglobulin domain. The intracellular segment of PTPμ has two PTP domains and a juxtamembrane segment that is homologous to the conserved intracellular domain of the cadherins. In cadherins, this segment interacts with proteins termed catenins to mediate association with the actin cytoskeleton. In this article, we demonstrate that PTPμ associates with a complex containing cadherins. α- and β-catenin in mink lung (MvLu) cells, and in rat heart, lung, and brain tissues. Greater than 80% of the cadherin in the cell is cleared from Triton X-100 lysates of MvLu cells after immunoprecipitation with antibodies to PTPμ; however, the complex is dissociated when lysates are prepared in more stringent, SDS-containing RIPA buffer. In vitro binding studies demonstrated that the intracellular segment of PTPμ binds directly to the intracellular domain of E-cadherin, but not to α- or β-catenin. Consistent with their ability to interact in vivo, PTPμ, cadherins, and catenins all localized to points of cell-cell contact in MvLu cells, as assessed by immunocytochemical staining. After pervanadate treatment of MvLu cells, which inhibits cellular tyrosine phosphatase activity including PTPμ, the cadherins associated with PTPμ are now found in a tyrosine-phosphorylated form, indicating that the cadherins may be an endogenous substrate for PTPμ. These data suggest that PTPμ may be one of the enzymes that regulates the dynamic tyrosine phosphorylation, and thus function, of the cadherin/catenin complex in vivo.