The protein tyrosine phosphatase PTP1B is required for efficient delivery of N-cadherin to the cell surface.

PTP1B bound to mature N-cadherin promotes the association of beta-catenin into the complex, the stable expression of the complex at cell surface, and cadherin-mediated adhesion. Here we show that PTP1B is also required for N-cadherin precursor trafficking through early stages of the secretory pathway. This function does not require association of PTP1B with the precursor. In PTP1B null cells, the N-cadherin precursor showed higher sensitivity to endoglycosidase H than in cells reconstituted with the wild-type enzyme. It also showed slower kinetics of ER-to-Golgi translocation and processing. Trafficking of the viral stomatitis vesicular glycoprotein, VSV-G, however, revealed no differences between PTP1B null and reconstituted cells. N-cadherin precursor complexes contained similar levels of alpha- and beta-catenin regardless of PTP1B expression. In contrast, the associated p120 catenin (p120) was significantly reduced in absence of PTP1B expression. An N-cadherin precursor construct defective in p120 binding, and expressed in PTP1B reconstituted cells, showed higher sensitivity to endoglycosidase H and slower kinetics of processing than the wild-type precursor. Our results suggest that PTP1B promotes the association of p120 to the N-cadherin precursor, facilitating the trafficking of the complex from the ER to the Golgi complex.