%0 Journal Article
%T Phosphatase of regenerating liver-3 directly interacts with integrin ¦Â1 and regulates its phosphorylation at tyrosine 783
%A Tian Wei
%A Qu Like
%A Meng Lin
%A Liu Caiyun
%J BMC Biochemistry
%D 2012
%I BioMed Central
%R 10.1186/1471-2091-13-22
%X 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 ¦Â1 in cancer cells. Recombinant PRL-3 associates with the intracellular domain of integrin ¦Â1 in vitro. Silencing of integrin ¦Á1 enhances PRL-3-integrin ¦Â1 interaction. Furthermore, PRL-3 diminishes tyrosine phosphorylation of integrin ¦Â1 in vitro and in vivo. With site-specific anti-phosphotyrosine antibodies against residues in the intracellular domain of integrin ¦Â1, 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 ¦Á1 decreases the phosphorylation of this site. Conclusions Our results revealed a direct interaction between PRL-3 and integrin ¦Â1 and characterized Y783 of integrin ¦Â1 as a bona fide substrate of PRL-3, which is negatively regulated by integrin ¦Á1.
%K PRL-3
%K tyrosine phosphatase
%K integrin ¦Â1
%K dephosphorylation
%U http://www.biomedcentral.com/1471-2091/13/22