C-Src-mediated phosphorylation of δ-catenin increases its protein stability and the ability of inducing nuclear distribution of β-catenin

Although delta-catenin was first considered as a brain specific protein, strong evidence of delta-catenin overexpression in various cancers, including prostate cancer, has been accumulated. Phosphorylation of delta-catenin by Akt and GSK3 beta has been studied in various cell lines. However, tyrosine phosphorylation of delta-catenin in prostate cancer cells remains unknown. In the current study, we demonstrated that Src kinase itself phosphorylates delta-catenin on its tyrosine residues in prostate cancer cells and further illustrated that Y1073, Y1112 and Y1176 of delta-catenin are predominant sites responsible for tyrosine phosphoiylation mediated by c-Src. Apart from c-Src, other Src family kinases, including Fgr, Fyn and Lyn, can also phosphorylate delta-catenin. We also found that c-Src-mediated Tyr-phosphorylation of delta-catenin increases its stability via decreasing its affinity to GSK3 beta and enhances its ability of inducing nuclear distribution of beta-catenin through interrupting the integrity of the E-cadherin. Taken together, these results indicate that c-Src can enhance the oncogenic function of delta-catenin in prostate cancer cells. (C) 2014 Elsevier B.V. All rights reserved.