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

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• 作者：Yongfeng He^a ; Hangun Kim^b ; Taeyong Ryu^a ; Kwang-Youl Lee^a ; Won-Seok Choi^c ; Kyeong-Man Kim^a ; Mei Zheng^a ; Yechan Joh^c ; Jae-Hyuk Lee^d ; Dong-Deuk Kwon^d ; Qun Lu^e ; Kwonseop Kim^a ; ^d ; ^{koskim@chonnam.ac.kr" class="auth_mail}
• 关键词：未-Catenin ; c-Src ; Tyrosine phosphorylation ; GSK3 ; E-cadherin
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：April, 2014
• 年：2014
• 卷：1843
• 期：4
• 页码：758-768
• 全文大小：1361 K

文摘

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