Publication Date:
2012-10-24
Description:
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 beta1 in cancer cells. Recombinant PRL-3 associates with the intracellular domain of integrin beta1 in vitro. Silencing of integrin alpha1 enhances PRL-3-integrin beta1 interaction. Furthermore, PRL-3 diminishes tyrosine phosphorylation of integrin beta1 in vitro and in vivo. With site-specific anti-phosphotyrosine antibodies against residues in the intracellular domain of integrin beta1, 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 chemical inhibitor of PRL-3. Conversely, depletion of integrin alpha1 decreases the phosphorylation of this site. Conclusions: Our results revealed a direct interaction between PRL-3 and integrin beta1 and characterized Y783 of integrin beta1 as a bona fide substrate of PRL-3, which is negatively regulated by integrin alpha1.
Electronic ISSN:
1471-2091
Topics:
Chemistry and Pharmacology
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