...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Activated PAK4 Regulates Cell Adhesion and Anchorage-Independent Growth
【24h】

Activated PAK4 Regulates Cell Adhesion and Anchorage-Independent Growth

机译：激活的PAK4调节细胞粘附和锚定非依赖性生长

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The serine/threonine kinase PAK4 is an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family in both sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Since previous characterization of PAK4 was carried out only with the wild-type kinase, we have generated a constitutively active mutant of the kinase to determine whether it has other functions. Expression of activated PAK4 in fibroblasts led to a transient induction of filopodia, which is consistent with its role as an effector for Cdc42. In addition, use of the activated mutant revealed a number of other important functions of this kinase that were not revealed by studying the wild-type kinase. For example, activated PAK4 led to the dissolution of stress fibers and loss of focal adhesions. Consequently, cells expressing activated PAK4 had a defect in cell spreading onto fibronectin-coated surfaces. Most importantly, fibroblasts expressing activated PAK4 had a morphology that was characteristic of oncogenic transformation. These cells were anchorage independent and formed colonies in soft agar, similar to what has been observed previously in cells expressing activated Cdc42. Consistent with this, dominant-negative PAK4 mutants inhibited focus formation by oncogenic Dbl, an exchange factor for Rho family GTPases. These results provide the first demonstration that a PAK family member can transform cells and indicate that PAK4 may play an essential role in oncogenic transformation by the GTPases. We propose that the morphological changes and changes in cell adhesion induced by PAK4 may play a direct role in oncogenic transformation by Rho family GTPases and their exchange factors.
机译：丝氨酸/苏氨酸激酶PAK4是Rho GTPase Cdc42的效应分子。 PAK4在序列和功能上与PAK家族的其他成员不同。以前我们已经表明，该激酶的重要功能是响应激活的Cdc42介导丝状伪足的诱导。由于以前仅用野生型激酶进行了PAK4的表征，因此我们已经生成了该激酶的组成型活性突变体，以确定其是否具有其他功能。活化的PAK4在成纤维细胞中的表达导致丝状伪足的短暂诱导，这与其作为Cdc42的效应子的作用是一致的。另外，使用活化的突变体揭示了该激酶的许多其他重要功能，而通过研究野生型激酶并未揭示这些功能。例如，活化的PAK4导致应力纤维的溶解和粘着力的损失。因此，表达活化的PAK4的细胞在铺展到纤连蛋白包被的表面上具有缺陷。最重要的是，表达活化的PAK4的成纤维细胞的形态具有致癌性转化的特征。这些细胞独立于锚定并在软琼脂中形成集落，类似于先前在表达活化的Cdc42的细胞中观察到的情况。与此相一致，显性阴性PAK4突变体通过致癌性Dbl（Rho家族GTPase的交换因子）抑制了焦点形成。这些结果首次证明了PAK家族成员可以转化细胞，并表明PAK4可能在GTPases的致癌转化中起重要作用。我们建议形态变化和PAK4诱导的细胞粘附变化可能在Rho家族GTPases及其交换因子的致癌转化中起直接作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号