Phosphorylation of adducin by protein kinase Cδ promotes cell motility
Phosphorylation of adducin by protein kinase Cδ promotes cell motility
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DOI：
10.1242/jcs.03408
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Chen, Hong-Chen
中科院分区：
文献类型：
--
作者：
Chen, Chien-Lin;Hsieh, Yeun-Ting;Chen, Hong-Chen
蛋白激酶C δ（PKC δ）在细胞增殖、分化和凋亡中发挥关键作用。在这项研究中，我们研究了PKC δ的作用，细胞运动使用Madin-达比犬肾细胞。PKC δ的过表达促进膜突起，伴随着细胞运动性的增加。相比之下，RNA干扰抑制PKC δ表达抑制细胞运动。此外，PKC δ的一小部分被检测到在膜突起的边缘，其中它与内收蛋白共定位，内收蛋白是一种膜骨架蛋白，其磷酸化状态是重要的皮质肌动蛋白细胞骨架的重塑。在完整细胞中，PKC δ表达升高与内收蛋白Ser 726磷酸化增加相关。在体外，PKC δ，而不是PKC δ，直接磷酸化Ser 726的内收蛋白。最后，我们证明了内收蛋白和PKC δ的过表达可以产生促进细胞铺展和细胞迁移的协同作用。我们的研究结果支持PKC δ在细胞运动中的积极作用，并强烈建议PKC δ活性，内收蛋白磷酸化和细胞运动之间的联系。
Protein kinase C delta (PKC delta) has been implicated to play a crucial role in cell proliferation, differentiation and apoptosis. In this study, we have investigated the role of PKC delta in cell motility using Madin- Darby canine kidney cells. Overexpression of PKC delta promoted membrane protrusions, concomitant with increased cell motility. By contrast, suppression of PKC delta expression by RNA interference inhibited cell motility. Moreover, a fraction of PKC delta was detected at the edge of membrane protrusions in which it colocalized with adducin, a membrane skeletal protein whose phosphorylation state is important for remodeling of the cortical actin cytoskeleton. Elevated expression of PKC delta correlated with increased phosphorylation of adducin at Ser726 in intact cells. In vitro, PKC delta, but not PKC delta, directly phosphorylated the Ser726 of adducin. Finally, we demonstrated that overexpression of both adducin and PKC delta could generate a synergistic effect on promoting cell spreading and cell migration. Our results support a positive role for PKC delta in cell motility and strongly suggest a link between PKC delta activity, adducin phosphorylation and cell motility.