Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration.
Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration.
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DOI：
10.1371/journal.pone.0098090
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Storz P
中科院分区：
文献类型：
--
作者：
Döppler H;Bastea LI;Borges S;Spratley SJ;Pearce SE;Storz P
蛋白激酶D(PKD)通过p21激活的蛋白激酶4(PAK4)和磷酸酶弹弓蛋白1L(SSH1L)调节由cofilin驱动的肌动蛋白重组，并引导细胞迁移。不同的内源性PKD亚型对这两条信号通路的相对贡献还没有被充分阐明。我们在这里分析了两个细胞株(HeLa和MDA-MB-468)，它们表达蛋白激酶D2(PKD2)和蛋白激酶D3(PKD3)。我们发现，在正常生长条件下，两种异构体都可以形成一个复合体，其中PKD3是碱性活性的，而PKD2是非活性的。PKD3的基础活性介导了PAK4活性和下游信号转导，但对SSH1L没有明显的抑制作用。这一信号星座是促进细胞定向迁移所必需的。PKD2的激活和PKD3活性的进一步增加导致额外的磷酸化和内源性SSH1L的抑制。净效应是磷酸化核纤蛋白显著增加，细胞迁移减少，因为现在PAK4和SSH1L都由活性的PKD2/PKD3复合体调节。我们的数据表明，PKD复合体为两个cofilin调节通路提供了一个接口。依赖于相关的PKD酶的活性，信号可以被平衡以保证功能的COFILIN活性周期并增加细胞迁移，或者被失衡以减少细胞迁移。我们的数据还解释了PKD亚型如何在定向细胞迁移中介导不同的影响。
Protein kinase D (PKD) enzymes regulate cofilin-driven actin reorganization and directed cell migration through both p21-activated kinase 4 (PAK4) and the phosphatase slingshot 1L (SSH1L). The relative contributions of different endogenous PKD isoforms to both signaling pathways have not been elucidated, sufficiently. We here analyzed two cell lines (HeLa and MDA-MB-468) that express the subtypes protein kinase D2 (PKD2) and protein kinase D3 (PKD3). We show that under normal growth conditions both isoforms can form a complex, in which PKD3 is basally-active and PKD2 is inactive. Basal activity of PKD3 mediates PAK4 activity and downstream signaling, but does not significantly inhibit SSH1L. This signaling constellation was required for facilitating directed cell migration. Activation of PKD2 and further increase of PKD3 activity leads to additional phosphorylation and inhibition of endogenous SSH1L. Net effect is a dramatic increase in phospho-cofilin and a decrease in cell migration, since now both PAK4 and SSH1L are regulated by the active PKD2/PKD3 complex. Our data suggest that PKD complexes provide an interface for both cofilin regulatory pathways. Dependent on the activity of involved PKD enzymes signaling can be balanced to guarantee a functional cofilin activity cycle and increase cell migration, or imbalanced to decrease cell migration. Our data also provide an explanation of how PKD isoforms mediate different effects on directed cell migration.
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影响因子：
7.8
作者：
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影响因子：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1083/jcb.200401136
发表时间：
2004-05-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nagata-Ohashi K;Ohta Y;Goto K;Chiba S;Mori R;Nishita M;Ohashi K;Kousaka K;Iwamatsu A;Niwa R;Uemura T;Mizuno K
通讯作者：
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