Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
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DOI：
10.1152/ajpcell.00503.2006
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发表时间：
2007-06
期刊：
影响因子：
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通讯作者：
S. Sahu;S. Núñez;Guang Bai;Anandarup Gupta
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文献类型：
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作者：
S. Sahu;S. Núñez;Guang Bai;Anandarup Gupta
我们已经鉴定出前列腺癌细胞中存在 leupaxin (LPXN)，它属于粘着斑相关接头蛋白的桩蛋白大家族。先前的研究表明，LPXN 是破骨细胞中发现的足体信号复合物的一个组成部分，其中 LPXN 被发现与蛋白酪氨酸激酶 Pyk2 和 c-Src 以及胞质蛋白酪氨酸磷酸酶 - 脯氨酸 - 谷氨酸 - 丝氨酸 - 和苏氨酸丰富的序列（PTP-PEST）相关。在当前的研究中，LPXN 在 PC-3 细胞（一种骨源性转移性前列腺癌细胞系）中可检测到 50 kDa 的蛋白质。在 PC-3 细胞中，LPXN 还被发现与 Pyk2、c-Src 和 PTP-PEST 相关。 siRNA 介导的 LPXN 抑制导致体外 PC-3 细胞迁移减少。重组腺病毒介导的 LPXN 过表达导致 Pyk2 与 LPXN 的关联增加，而类似的腺病毒介导的 PTP-PEST 过表达导致 Pyk2 和 c-Src 与 LPXN 的关联减少。通过体外 Transwell 迁移测定评估，PC-3 细胞中 LPXN 的过度表达导致迁移增加。相反，PC-3细胞中PTP-PEST的过度表达导致迁移减少。 LPXN 的过表达导致 Rho GTPase 活性增加，而在 PTP-PEST 过表达细胞中 Rho GTPase 活性降低。在 Rho GTPase 选择性抑制剂 Y27632 的存在下，LPXN 过度表达后 Rho GTPase 活性的增加受到抑制。总之，我们的数据表明 LPXN 与 Pyk2、c-Src 和 PTP-PEST 形成信号复合物来调节前列腺癌细胞的迁移。
We have identified the presence of leupaxin (LPXN), which belongs to the paxillin extended family of focal adhesion-associated adaptor proteins, in prostate cancer cells. Previous studies have demonstrated that LPXN is a component of the podosomal signaling complex found in osteoclasts, where LPXN was found to associate with the protein tyrosine kinases Pyk2 and c-Src and the cytosolic protein tyrosine phosphatase-proline-, glutamate-, serine-, and threonine-rich sequence (PTP-PEST). In the current study, LPXN was detectable as a 50-kDa protein in PC-3 cells, a bone-derived metastatic prostate cancer cell line. In PC-3 cells, LPXN was also found to associate with Pyk2, c-Src, and PTP-PEST. A siRNA-mediated inhibition of LPXN resulted in decreased in vitro PC-3 cell migration. A recombinant adenoviral-mediated overexpression of LPXN resulted in an increased association of Pyk2 with LPXN, whereas a similar adenoviral-mediated overexpression of PTP-PEST resulted in decreased association of Pyk2 and c-Src with LPXN. The overexpression of LPXN in PC-3 cells resulted in increased migration, as assessed by in vitro Transwell migration assays. On the contrary, the overexpression of PTP-PEST in PC-3 cells resulted in decreased migration. The overexpression of LPXN resulted in increased activity of Rho GTPase, which was decreased in PTP-PEST-overexpressing cells. The increase in Rho GTPase activity following overexpression of LPXN was inhibited in the presence of Y27632, a selective inhibitor of Rho GTPase. In conclusion, our data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells.