Src-mediated phosphorylation of the tyrosine phosphatase PRL-3 is required for PRL-3 promotion of Rho activation, motility and invasion.
Src-mediated phosphorylation of the tyrosine phosphatase PRL-3 is required for PRL-3 promotion of Rho activation, motility and invasion.
复制标题
DOI：
10.1371/journal.pone.0064309
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cox AD
中科院分区：
文献类型：
--
作者：
Fiordalisi JJ;Dewar BJ;Graves LM;Madigan JP;Cox AD
转移相关的酪氨酸磷酸酶PRL-3/PTP 4A在许多癌症中上调，但调节PRL-3活性的机制除了其表达水平外还没有研究。在这里，我们报告的证据都Src依赖的酪氨酸磷酸化的PRL-3和Src介导的调节PRL-3的生物活性。我们使用结构突变体、药理学抑制剂和siRNA来证明SW 480结肠癌细胞中内源性PRL-3的Src依赖性磷酸化。我们还证明，PRL-3没有酪氨酸磷酸化的SYF小鼠胚胎成纤维细胞缺乏Src，是和Fyn，除非Src被重新表达。此外，我们表明，血小板衍生生长因子（PDGF）可以刺激PRL-3磷酸化的Src依赖的方式。最后，我们表明，PRL-3诱导的细胞运动，基质胶入侵和激活的细胞色素调节小GTdR RhoC被废除的存在下，磷酸缺陷的PRL-3突变体Y 53 F，或通过使用Src抑制剂。因此，PRL-3需要Src激酶的活性，可能是Src本身，以促进这些癌症相关表型。我们的数据建立了一个模型的调节PRL-3的Src支持的可能性，其协调作用的信号通路促进侵袭和转移，并支持同时使用新的分子靶向治疗针对这些蛋白质。
The metastasis-associated tyrosine phosphatase PRL-3/PTP4A is upregulated in numerous cancers, but the mechanisms modulating PRL-3 activity other than its expression levels have not been investigated. Here we report evidence for both Src-dependent tyrosine phosphorylation of PRL-3 and Src-mediated regulation of PRL-3 biological activities. We used structural mutants, pharmacological inhibitors and siRNA to demonstrate Src-dependent phosphorylation of endogenous PRL-3 in SW480 colon cancer cells. We also demonstrated that PRL-3 was not tyrosine phosphorylated in SYF mouse embryo fibroblasts deficient in Src, Yes and Fyn unless Src was re-expressed. Further, we show that platelet-derived growth factor (PDGF) can stimulate PRL-3 phosphorylation in a Src-dependent manner. Finally, we show that PRL-3-induced cell motility, Matrigel invasion and activation of the cytoskeleton-regulating small GTPase RhoC were abrogated in the presence of the phosphodeficient PRL-3 mutant Y53F, or by use of a Src inhibitor. Thus, PRL-3 requires the activity of a Src kinase, likely Src itself, to promote these cancer-associated phenotypes. Our data establish a model for the regulation of PRL-3 by Src that supports the possibility of their coordinate roles in signaling pathways promoting invasion and metastasis, and supports simultaneous use of novel molecularly targeted therapeutics directed at these proteins.
登录
查看更多内容
影响因子：
5.2
作者：
Kong, Dejuan;Li, Yiwei;Wang, Zhiwei;Banerjee, Sanjeev;Ahmad, Aamir;Kim, Hyeong-Reh Choi;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
DOI：
10.1016/j.bbrc.2011.02.037
发表时间：
2011-03-11
影响因子：
3.1
作者：
Choi, Myung-Suk;Min, Sang-Hyun;Yoo, Ook-Joon
通讯作者：
Yoo, Ook-Joon
影响因子：
3.6
作者：
Guo, K;Li, J;Zeng, Q
通讯作者：
Zeng, Q
影响因子：
3.7
作者：
Dietrich, Karin-Almut;Schwarz, Rene;Giehl, Klaudia
通讯作者：
Giehl, Klaudia
影响因子：
2.8
作者：
Guzinska-Ustymowicz, Katarzyna;Pryczynicz, Anna
通讯作者：
Pryczynicz, Anna