Brady-Kalnay, S. M., Rimm, D. L., Tonks, N. K. (August 1995) Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo. Journal of Cell Biology, 130 (4). pp. 977-986. ISSN 0021-9525
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Abstract
The extracellular segment of the receptor-type protein tyrosine phosphatase PTP mu, possesses an MAM domain, an immunoglobulin domain, and four fibronectin type-III repeats. It binds homophilically, i.e., PTP mu on the surface of one cell binds to PTP mu on an apposing cell, and the binding site lies within the immunoglobulin domain. The intracellular segment of PTP mu 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 PTP mu associates with a complex containing cadherins, alpha- and beta-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 immuno-precipitation with antibodies to PTP mu; 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 PTP mu binds directly to the intracellular domain of E-cadherin, 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 immunocytochemical staining. After pervanadate treatment of MvLu cells, which inhibits cellular tyrosine phosphatase activity including PTP mu, the cadherins associated with PTP mu are now found in a tyrosine-phosphorylated 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 that regulates the dynamic tyrosine phosphorylation, and thus function, of the cadherin/catenin complex in vivo.
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