title: C-Src-mediated phosphorylation of δ-catenin increases its protein stability and the ability of inducing nuclear distribution of β-catenin.
abstract: Although δ-catenin was first considered as a brain specific protein, strong evidence of δ-catenin overexpression in various cancers, including prostate cancer, has been accumulated. Phosphorylation of δ-catenin by Akt and GSK3β has been studied in various cell lines. However, tyrosine phosphorylation of δ-catenin in prostate cancer cells remains unknown. In the current study, we demonstrated that Src kinase itself phosphorylates δ-catenin on its tyrosine residues in prostate cancer cells and further illustrated that Y1073, Y1112 and Y1176 of δ-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 δ-catenin. We also found that c-Src-mediated Tyr-phosphorylation of δ-catenin increases its stability via decreasing its affinity to GSK3β and enhances its ability of inducing nuclear distribution of β-catenin through interrupting the integrity of the E-cadherin. Taken together, these results indicate that c-Src can enhance the oncogenic function of δ-catenin in prostate cancer cells.
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: He
authors.affiliation: College of Pharmacy, Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Taeyong
authors.initials: T
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Kwang-Youl
authors.initials: KY
authors.lastname: Lee
authors.affiliation: School of Biological Sciences and Technology, College of Natural Sciences, College of Medicine, Chonnam National University, Gwangju, South Korea.
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Kyeong-Man
authors.initials: KM
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.affiliation: School of Biological Sciences and Technology, College of Natural Sciences, College of Medicine, Chonnam National University, Gwangju, South Korea.
authors.forename: Yechan
authors.initials: Y
authors.lastname: Joh
authors.affiliation: Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Dong-Deuk
authors.initials: DD
authors.lastname: Kwon
authors.affiliation: Department of Anatomy and Cell Biology, The Brody School of Medicine, East Carolina University, Greenville, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea; Chonnam National University Hospital, Gwangju, South Korea. Electronic address: koskim@chonnam.ac.kr.
authors.forename: Kwonseop
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D051176:beta Catenin; D014443:Tyrosine; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000095002:Delta Catenin
keywords: E-cadherin; GSK3; Tyrosine phosphorylation; c-Src; δ-Catenin