Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot.
Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot.
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DOI：
10.1038/ncb1861
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发表时间：
2009-05
影响因子：
21.3
通讯作者：
Storz P
中科院分区：
文献类型：
--
作者：
Eiseler T;Döppler H;Yan IK;Kitatani K;Mizuno K;Storz P
动态肌动蛋白重塑过程中的前沿迁移的肿瘤细胞是协调一致的事件控制的微调时间和空间的相互作用的激酶和磷酸酶。肌动蛋白切割由ADF/Cofilin调节，其调节刺激诱导的板状伪足突出和定向细胞运动。丝切蛋白通过经由弹弓（SSH）家族的磷酸酶的去磷酸化而活化。SSH活性强烈增加其结合到丝状肌动蛋白（F-肌动蛋白），然而，其他上游调控仍然未知。我们表明，在响应RhoA激活，蛋白激酶D1（PKD 1）磷酸化的SSH酶SSH 1 L在位于其肌动蛋白结合基序的丝氨酸残基。这产生了一个14-3-3结合基序，通过将SSH 1 L隔离在细胞质中来阻断SSH 1 L定位于板状伪足中富含F-肌动蛋白的结构。因此，在侵袭性肿瘤细胞中组成型活性PKD 1的表达增强了cofilin的磷酸化，并有效地阻断了游离肌动蛋白丝倒刺末端的形成并指导了细胞迁移。
Dynamic actin remodelling processes at the leading edge of migrating tumour cells are concerted events controlled by a fine-tuned temporal and spatial interplay of kinases and phosphatases. Actin severing is regulated by ADF/Cofilin which regulates stimulus-induced lamellipodia protrusion and directed cell motility. Cofilin is activated by dephosphorylation via phosphatases of the slingshot (SSH) family. SSH activity is strongly increased by its binding to filamentous actin (F-actin), however, other upstream regulators remain unknown. We show that in response to RhoA activation, Protein Kinase D1 (PKD1) phosphorylates the SSH enzyme SSH1L at a serine residue located in its actin binding motif. This generates a 14-3-3 binding motif, blocks the localization of SSH1L to F-actin-rich structures in the lamellipodium by sequestering it in the cytoplasm. Consequently, expression of constitutively-active PKD1 in invasive tumour cells enhanced phosphorylation of cofilin and effectively blocked the formation of free actin filament barbed ends and directed cell migration.
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影响因子：
4.8
作者：
Rey, O;Sinnett-Smith, J;Rozengurt, E
通讯作者：
Rozengurt, E
影响因子：
9.2
作者：
Ichetovkin, I;Grant, W;Condeelis, J
通讯作者：
Condeelis, J
影响因子：
7.8
作者：
Mouneimne, Ghassan;Soon, Lilian;DesMarais, Vera;Sidani, Mazen;Song, Xiaoyan;Yip, Shu-Chin;Ghosh, Mousumi;Eddy, Robert;Backer, Jonathan M;Condeelis, John
通讯作者：
Condeelis, John
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：
Mizuno K
影响因子：
3.5
作者：
Eiseler, Tim;Schmid, Michael A.;Hausser, Angelika
通讯作者：
Hausser, Angelika