H1 and PAR-2 receptors interrupt E-cadherin adhesion and compromise transepithelial resistance (TER). Cadherin adhesion depends on the association of cadherin with beta-catenin, and this association may be regulated by phosphorylation of tyrosines in beta-catenin. We hypothesized that loss of cadherin adhesion and compromise of TER by H1 or PAR2 requires phosphorylation of tyrosines in beta-catenin. L-cells were stably transfected to express E-cadherin (L-E-cad cells) and H1 (L-H1-E-cad cells). L-cells and MDCK cells express PAR2. L-E-cad, L-H1-E-cad and MDCK cells were stably transfected with wild type (wt) or mutant beta-catenin, converting tyrosine 142, 489 or 654 to phenylalanine (Y142F, Y489F or Y654F). H1 and PAR2 interrupted adhesion to immobilized E-cadherin-Fc fusion protein of cells expressing wt or Y142F beta-catenin, but did not interrupt adhesion of cells expressing Y489F or Y654F beta-catenin. PAR2 activation decreased the TER of MDCK cells expressing wt or Y142F beta-catenin, but did not decrease the TER of MDCK cells expressing Y489F or Y654F beta-catenin. The tyrosine phosphatase, PTP1B, binds to E-cadherin and dephosphorylates beta-catenin. Inhibition of PTP1B interrupted adhesion to E-cadherin-Fc of MDCK cells expressing wt beta-catenin, but did not affect adhesion of MDCK cells expressing Y489F or Y654F beta-catenin. Inhibition of PTP1B compromised the TER of MDCK cells expressing wt beta-catenin, but did not affect the TER of cells expressing Y489F or Y654F beta-catenin. H1 and PAR2 interrupt E-cadherin adhesion by phosphorylating Y489 and Y654 in beta-catenin. Activation of PAR2, has no effect on the TER without first interrupting E-cadherin adhesion.