Receptor protein-tyrosine phosphatase RPTPμ binds to and dephosphorylates the catenin p120ctn

RPTP mu is a prototypic receptor-like protein-tyrosine phosphatase (RPTP) that mediates homotypic cell-cell interactions. Intracellularly, RPTP mu consists of a relatively large juxtamembrane region and two phosphatase domains, but little is still known about its substrate(s). Here we show that RPTP mu associates with the catenin p120(ctn), a tyrosine kinase substrate and an interacting partner of cadherins, No interaction is detectable between RPTP mu and beta-catenin, Furthermore, we show that tyrosine-phosphorylated p120(ctn) is dephosphorylated by RPTP mu both in vitro and in intact cells. Complex formation between RPTP mu and p120(ctn) does not require tyrosine phosphorylation of p120(ctn), Mutational analysis reveals that both the juxtamembrane region and the second phosphatase domain of RPTP mu are involved in p120(ctn) binding. The RPTP mu-interacting domain of p120(ctn) maps to its unique N terminus, a region distinct from the cadherin-interacting domain. A mutant form of p120(ctn) that fails to bind cadherins can still associate with RPTP mu. Our findings indicate that RPTP mu interacts with p120(ctn) independently of cadherins, and they suggest that this interaction may serve to control the tyrosine phosphorylation state of p120(ctn) at sites of cellcell contact.