Defining the function of β‐catenin tyrosine phosphorylation in cadherin‐mediated cell–cell adhesion

Abstract

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.

Epidermal Growth Factor Receptor/β-Catenin/T-Cell Factor 4/Matrix Metalloproteinase 1: A New Pathway for Regulating Keratinocyte Invasiveness after UVA Irradiation

“…Previous studies have described that h-catenin tyrosine phosphorylation may result in its relocalization from the membrane to the nucleus (19)(20)(21). Therefore, we hypothesized that UVA could induce EGFRdependent h-catenin nuclear redistribution.…”

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway

“…In addition, colocalization of caveolin-1 and b-catenin was observed (Figure 4a). Therefore, overexpression of caveolin-1 might stabilize the E-cadherin/b-catenin complex on membranes by suppressing the phosphorylation of b-catenin, which negatively regulate the interaction between E-cadherin and b-catenin (Piedra et al, 2003;Lee et al, 2007;Tominaga et al, 2008).…”

Role of Janus Kinase 3 in Mucosal Differentiation and Predisposition to Colitis

“…Although phosphorylation of tyrosine 142 of ␤-catenin facilitates its participation in transcription factor activity, phosphorylation of tyrosine 654 decreases intramolecular association between the C-terminal tail and the armadillo repeat domain, where armadillo repeat domain facilitates ␤-catenin interactions with E-cadherin (38,51). Moreover, the phosphomimetic mutant Y654E of ␤-catenin that mimics constitutive phosphorylation at tyrosine 654 forms a functional cadherin-catenin complex to mediate strong cell adhesion (52). Our data suggest that phosphorylation of 654 and not of 142 was important for ␤-catenin interactions with Jak3 upon Jak3 activation.…”