PCP-2 is a human receptor-like protein tyrosine phosphatase and a member of the MAM domain family cloned in human pancreatic adenocarcinoma cells. Previous studies showed that PCP-2 directly interacted with beta-catenin through the juxtamembrane domain, dephosphorylated beta-catenin and played an important role in the regulation of cell adhesion. Recent study showed that PCP-2 was also involved in the repression of beta-catenin-induced transcriptional activity. Here we describe the interactions of PCP-2 with the beta3A subunit of adaptor protein (AP)-3 and sorting nexin (SNX) 3. These protein complexes were detected using the yeast two-hybrid assay with the juxtamembrane and membrane-proximal catalytic domain of PCP-2 as "bait" Both AP-3 and SNX3 are molecules involved in intracellular trafficking of membrane receptors. The association between the beta3A subunit of AP-3 and PCP-2 was further confirmed in mammalian cells. Our results suggested a possible mechanism of intracellular trafficking of PCP-2 mediated by AP-3 and SNX3 which might participate in the regulation of PCP-2 functions.