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首页> 外文期刊>Molecular and Cellular Biology >Pak1 and Pak2 Mediate Tumor Cell Invasion through Distinct Signaling Mechanisms
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Pak1 and Pak2 Mediate Tumor Cell Invasion through Distinct Signaling Mechanisms

机译：Pak1和Pak2通过不同的信号传导机制介导肿瘤细胞侵袭。

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Pak kinases are thought to play critical roles in cell migration and invasion. Here, we analyze the roles of Pak1 and Pak2 in breast carcinoma cell invasion using the transient transfection of small interfering RNA. We find that although both Pak1 and Pak2 contribute to breast carcinoma invasion stimulated by heregulin, these roles are mediated by distinct signaling mechanisms. Thus, whereas the depletion of Pak1 interferes with the heregulin-mediated dephosphorylation of cofilin, the depletion of Pak2 does not. The depletion of Pak1 also has a stronger inhibitory effect on lamellipodial protrusion than does the depletion of Pak2. Interestingly, Pak1 and Pak2 play opposite roles in regulating the phosphorylation of the myosin light chain (MLC). Whereas the depletion of Pak1 decreases phospho-MLC levels in heregulin-stimulated cells, the depletion of Pak2 enhances MLC phosphorylation. Consistent with their opposite effects on MLC phosphorylation, Pak1 and Pak2 differentially modulate focal adhesions. Pak2-depleted cells display an increase in focal adhesion size, whereas in Pak1-depleted cells, focal adhesions fail to mature. We also found that the depletion of Pak2, but not Pak1, enhances RhoA activity and that the inhibition of RhoA signaling in Pak2-depleted cells decreases MLC phosphorylation and restores cell invasion. In summary, this work presents the first comprehensive analysis of functional differences between the Pak1 and Pak2 isoforms.
机译：Pak激酶被认为在细胞迁移和侵袭中起关键作用。在这里，我们使用小干扰RNA的瞬时转染来分析Pak1和Pak2在乳腺癌细胞侵袭中的作用。我们发现，尽管Pak1和Pak2都参与调蛋白刺激的乳腺癌浸润，但这些作用是由不同的信号传导机制介导的。因此，尽管Pak1的消耗会干扰调蛋白介导的cofilin的去磷酸化，但Pak2的消耗却不会。与Pak2的消耗相比，Pak1的消耗对层状脂质体的突出也具有更强的抑制作用。有趣的是，Pak1和Pak2在调节肌球蛋白轻链（MLC）的磷酸化中起相反的作用。 Pak1的消耗减少了调蛋白刺激细胞中的磷酸化-MLC水平，而Pak2的消耗则增强了MLC磷酸化。与它们对MLC磷酸化的相反作用一致，Pak1和Pak2差异调节粘着斑。 Pak2耗尽的细胞显示出粘着斑大小的增加，而在Pak1耗尽的细胞中，粘着斑无法成熟。我们还发现Pak2的耗竭，而不是Pak1的耗竭，增强了RhoA活性，并且在Pak2耗竭的细胞中RhoA信号的抑制作用降低了MLC磷酸化并恢复了细胞入侵。总之，这项工作是对Pak1和Pak2同工型之间功能差异的首次综合分析。

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