Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation.
Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation.
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DOI：
10.1083/jcb.200405156
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发表时间：
2004-08-30
影响因子：
7.8
通讯作者：
Condeelis, John
中科院分区：
文献类型：
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作者：
Mouneimne, Ghassan;Soon, Lilian;DesMarais, Vera;Sidani, Mazen;Song, Xiaoyan;Yip, Shu-Chin;Ghosh, Mousumi;Eddy, Robert;Backer, Jonathan M;Condeelis, John
表皮生长因子（EGF）诱导的自由倒刺末端的增加，导致肌动蛋白聚合在癌细胞中的板状伪足的前缘，发生作为两个瞬变：早期的1分钟和晚期的3分钟。我们的研究结果表明，磷脂酶（PLC）是需要触发早期倒刺末端瞬变。磷酸肌醇-3激酶选择性调节晚期倒刺末端瞬时。PLC的抑制抑制cofilin活性在细胞中的早期瞬态，延迟突起的开始，并抑制细胞的能力，以感觉梯度的EGF。使用小干扰RNA沉默或功能阻断抗体抑制cofilin，选择性地抑制早期瞬时。因此，我们的研究结果表明，早期PLC和cofilin依赖的倒刺末端瞬态是需要的突起的启动，并参与设置响应EGF的细胞运动的方向。
The epidermal growth factor (EGF)–induced increase in free barbed ends, resulting in actin polymerization at the leading edge of the lamellipodium in carcinoma cells, occurs as two transients: an early one at 1 min and a late one at 3 min. Our results reveal that phospholipase (PLC) is required for triggering the early barbed end transient. Phosphoinositide-3 kinase selectively regulates the late barbed end transient. Inhibition of PLC inhibits cofilin activity in cells during the early transient, delays the initiation of protrusions, and inhibits the ability of cells to sense a gradient of EGF. Suppression of cofilin, using either small interfering RNA silencing or function-blocking antibodies, selectively inhibits the early transient. Therefore, our results demonstrate that the early PLC and cofilin-dependent barbed end transient is required for the initiation of protrusions and is involved in setting the direction of cell movement in response to EGF.