Latreille Mathieu, Abu-Thuraia Afnan, Oliva Rossella, Zuo Dongmei, Larose Louise
Polypeptide Laboratory, Department of Medicine, McGill University, Montreal, QC, Canada H3A 2B2.
Int J Cell Biol. 2012;2012:684684. doi: 10.1155/2012/684684. Epub 2012 Mar 7.
Actin cytoskeleton remodeling is under the regulation of multiple proteins with various activities. Here, we demonstrate that the γ2 isoform of Casein Kinase I (CKIγ2) is part of a novel molecular path regulating the formation of actin stress fibers. We show that overexpression of CKIγ2 in fibroblasts alters cell morphology by impairing actin stress fibers formation. We demonstrate that this is concomitant with increased phosphorylation of the CDK inhibitor p27(Kip) and lower levels of activated RhoA, and is dependent on CKIγ2 catalytic activity. Moreover, we report that roscovitine, a potent inhibitor of cyclin-dependent kinases, including Cdk5, decreases p27(Kip) protein levels and restores actin stress fibers formation in CKIγ2 overexpressing cells, suggesting the existence of a CKIγ2-Cdk5-p27(Kip)-RhoA pathway in regulating actin remodeling. On the other hand, we also show that in a manner independent of its catalytic activity, CKIγ2 delays cell cycle progression through G1. Collectively our findings reveal that CKIγ2 is a novel player in the control of actin cytoskeleton dynamics and cell proliferation.
肌动蛋白细胞骨架重塑受多种具有不同活性的蛋白质调控。在此，我们证明酪蛋白激酶I的γ2亚型（CKIγ2）是调控肌动蛋白应力纤维形成的新分子途径的一部分。我们表明，在成纤维细胞中过表达CKIγ2会通过损害肌动蛋白应力纤维的形成来改变细胞形态。我们证明，这与细胞周期蛋白依赖性激酶抑制剂p27（Kip）磷酸化增加以及活化的RhoA水平降低同时发生，并且依赖于CKIγ2的催化活性。此外，我们报告说，包括Cdk5在内的细胞周期蛋白依赖性激酶的有效抑制剂roscovitine可降低p27（Kip）蛋白水平，并在过表达CKIγ2的细胞中恢复肌动蛋白应力纤维的形成，这表明在调控肌动蛋白重塑中存在CKIγ2-Cdk5-p27（Kip）-RhoA途径。另一方面，我们还表明，CKIγ2以与其催化活性无关的方式延迟细胞周期通过G1期的进程。我们的研究结果共同表明，CKIγ2是控制肌动蛋白细胞骨架动力学和细胞增殖的新因子。
