Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.
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DOI:
10.1371/journal.pone.0021732
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Parker PJ
Parker PJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lachmann S;Jevons A;De Rycker M;Casamassima A;Radtke S;Collazos A;Parker PJ

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丝氨酸/苏氨酸激酶的哺乳动物蛋白激酶N(PKN)家族包含三种同种型,其是Rho家族GTP酶的靶标。小GTP酶是细胞骨架的主要调节剂,引起了对特定PKN亚型在细胞迁移和侵袭等过程中的作用的兴趣。据报道,PKN 3是前列腺肿瘤细胞侵袭所必需的,而PKN 1或2不是。在这里,我们采用了一个细胞模型,5637膀胱肿瘤细胞系PKN 2是相对高度表达,以评估这些亚型在迁移反应的潜在冗余。已经确定PKN 2在这些细胞的迁移和侵袭中具有关键作用。此外,使用PKN野生型和嵌合体的救援策略,它表明,PKN异构体不是简单的冗余支持迁移,但似乎是通过异构体特异性的调节结构域的特性,选择性上游信号。它的结论是,PKN的干预可能需要针对多种亚型,在不同的细胞类型是有效的。
The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.
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