Phosphatase of regenerating liver-3 directly interacts with integrin β1 and regulates its phosphorylation at tyrosine 783.
Phosphatase of regenerating liver-3 directly interacts with integrin β1 and regulates its phosphorylation at tyrosine 783.
复制标题
DOI：
10.1186/1471-2091-13-22
复制
发表时间：
2012-10-23
期刊：
影响因子：
--
通讯作者：
Shou C
中科院分区：
文献类型：
--
作者：
Tian W;Qu L;Meng L;Liu C;Wu J;Shou C
再生肝磷酸酶-3 （PRL-3或PTP4A3）与控制癌细胞增殖、运动、转移和血管生成有关。PRL-3的不正常表达与癌症进展高度相关，并预示较差的生存。虽然PRL-3被归类为酪氨酸磷酸酶，但其细胞底物仍然未知。我们证明了PRL-3在癌细胞中与整合素β1相互作用。重组PRL-3在体外与整合素β1的胞内结构域结合。整合素α1的沉默增强了prl -3-整合素β1的相互作用。此外，PRL-3在体外和体内均能降低整合素β1的酪氨酸磷酸化。在针对整合素β1胞内结构域残基的位点特异性抗磷酸酪氨酸抗体中，PRL-3以催化活性依赖的方式使酪氨酸-783（而非酪氨酸-795）去磷酸化。Y783的磷酸化通过消融PRL-3或用PRL-3的化学抑制剂治疗而增强。相反，整合素α1的缺失会降低该位点的磷酸化。我们的研究结果揭示了PRL-3与整合素β1之间的直接相互作用，并表征了整合素β1的Y783是PRL-3的真正底物，而PRL-3受整合素α1的负调控。
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. 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. 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.
登录
查看更多内容
PRL-3 通过 PRL-3-整合素 beta1-ERK1/2 和-MMP2 信号传导促进 LoVo 结肠癌细胞的运动、侵袭和转移。
影响因子：
37.3
作者：
Peng L;Xing X;Li W;Qu L;Meng L;Lian S;Jiang B;Wu J;Shou C
通讯作者：
Shou C
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
PLANTEFABER, LC;HYNES, RO
通讯作者：
HYNES, RO
DOI：
10.1016/j.bbamcr.2007.11.004
发表时间：
2008-02-01
影响因子：
5.1
作者：
Forte, Eleonora;Orsatti, Laura;Tomei, Licia
通讯作者：
Tomei, Licia
影响因子：
11.5
作者：
Kato, H;Semba, S;Yokozaki, H
通讯作者：
Yokozaki, H