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β-catenin is a key protein in cadherin–catenin cell adhesion complex and its tyrosine phosphorylation is believed to cause destruction of junctional apparatus. The broad spectrum of substrates for kinases and phosphatases, however, does not rule out tyrosine phosphorylation of other junctional proteins as the main culprit in reduction of cell adhesion activity. Further, the endogenous β-catenin perturbs detailed functional analysis of phosphorylated mutant β-catenin in living cells. To directly evaluate the effect of β-catenin tyrosine phosphorylation in cell adhesion, we utilized F9 cells in which expression of endogenous β-catenin and its closely related protein plakoglobin were completely shut down. We also used α-catenin-deficient (αD) cells to evaluate the role of α-catenin on β-catenin tyrosine phosphorylation. We show that β-catenin with phosphorylation mutation at 654th tyrosine forms functional cadherin–catenin complex to mediate strong cadherin-mediated cell adhesion. Moreover, we show that 64th and 86th tyrosines are mainly phosphorylated in F9 cells, especially in the absence of α-catenin. Phosphorylation of these tyrosine residues, however, does not affect cadherin-mediated cell adhesion activity. Our data identified a novel site phosphorylated by endogenous tyrosine kinases in β-catenin. We also demonstrate that tyrosine phosphorylation of β-catenin might regulate cadherin-mediated cell adhesion in a more complicated way than previously expected.