title: Phosphatase of regenerating liver-3 directly interacts with integrin β1 and regulates its phosphorylation at tyrosine 783.
abstract: BACKGROUND
  Phosphatase of regenerating liver-3 (PRL-3 or PTP4A3) has been implicated in controlling cancer cell proliferation, motility, metastasis, and angiogenesis. Deregulated expression of PRL-3 is highly correlated with cancer progression and predicts poor survival. Although PRL-3 was categorized as a tyrosine phosphatase, its cellular substrates remain largely unknown.
  
  
  RESULTS
  We demonstrated that PRL-3 interacts with integrin β1 in cancer cells. Recombinant PRL-3 associates with the intracellular domain of integrin β1 in vitro. Silencing of integrin α1 enhances PRL-3-integrin β1 interaction. Furthermore, PRL-3 diminishes tyrosine phosphorylation of integrin β1 in vitro and in vivo. With site-specific anti-phosphotyrosine antibodies against residues in the intracellular domain of integrin β1, tyrosine-783, but not tyrosine-795, is shown to be dephosphorylated by PRL-3 in a catalytic activity-dependant manner. Phosphorylation of Y783 is potentiated by ablation of PRL-3 or by treatment with a chemical inhibitor of PRL-3. Conversely, depletion of integrin α1 decreases the phosphorylation of this site.
  
  
  CONCLUSIONS
  Our results revealed a direct interaction between PRL-3 and integrin β1 and characterized Y783 of integrin β1 as a bona fide substrate of PRL-3, which is negatively regulated by integrin α1.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.forename: Caiyun
authors.initials: C
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D045744:Cell Line, Tumor; D045325:HCT116 Cells; D006801:Humans; D039423:Integrin alpha1 / Q000378:metabolism; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D039423:Integrin alpha1; D019012:Integrin beta1; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014443:Tyrosine; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases