Reif K, Nobes C D, Thomas G, Hall A, Cantrell D A
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, UK.
Curr Biol. 1996 Nov 1;6(11):1445-55. doi: 10.1016/s0960-9822(96)00749-x.
Phosphatidylinositol 3'-hydroxyl kinase (PI 3-kinase) is activated by many growth factor receptors and is thought to exert its cellular functions through the elevation of phosphatidylinositol (3,4,5)-triphosphate levels in the cell. PI 3-kinase is required for growth-factor induced changes of the actin cytoskeleton which are mediated by the GTPases Rac and Rho. Recently, a role for Rac and Rho in regulating gene transcription has become evident.
Here, we show that membrane targeting of the p110 catalytic subunit, but not the p85 regulatory subunit, of PI 3-kinase generates a constitutively active enzyme that allows us to assess the relative contribution of PI 3-kinase activation to a particular cellular response. Expression of this active PI 3-kinase induced actin reorganization in the form of Rac-mediated lamellipodia and focal complexes, and Rho-mediated stress fibres and focal adhesions. However, expression of active PI 3-kinase did not induce the Ras/Rac/Rho signalling pathways that regulate gene transcription controlled by the c-fos promoter, the c-fos serum response element or the transcription factors Elk-1 and AP-1.
Our results demonstrate that PI 3-kinase induces a selective subset of cellular responses, but is not sufficient to stimulate the full repertoire of Rac- or Rho-mediated responses.
磷脂酰肌醇3'-羟基激酶（PI 3激酶）被多种生长因子受体激活，并且被认为通过提高细胞内磷脂酰肌醇（3,4,5）-三磷酸水平来发挥其细胞功能。PI 3激酶是生长因子诱导的肌动蛋白细胞骨架变化所必需的，这些变化由GTP酶Rac和Rho介导。最近，Rac和Rho在调节基因转录中的作用已变得明显。
在此，我们表明PI 3激酶的p110催化亚基而非p85调节亚基的膜靶向产生了一种组成型活性酶，这使我们能够评估PI 3激酶激活对特定细胞反应的相对贡献。这种活性PI 3激酶的表达诱导了肌动蛋白重组，表现为Rac介导的片状伪足和粘着斑复合体，以及Rho介导的应力纤维和粘着斑。然而，活性PI 3激酶的表达并未诱导调节由c-fos启动子、c-fos血清反应元件或转录因子Elk-1和AP-1控制的基因转录的Ras/Rac/Rho信号通路。
我们的结果表明，PI 3激酶诱导细胞反应的一个选择性子集，但不足以刺激Rac或Rho介导的全部反应。
