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PAK1 and PAK2 have different roles in HGF-induced morphological responses

机译:PAK1和PAK2在HGF诱导的形态学反应中具有不同的作用

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摘要

Hepatocyte growth factor (HGF) stimulates dissociation of epithelial cells (scattering) and cell migration. Several Rho GTPases are required for HGF-induced scattering. PAK1 and PAK2 are members of the p21-activated kinase (PAK) family of serine/threonine kinases, and are activated by the Rho GTPases Rac and Cdc42. Here we investigate the contributions of PAK1 and PAK2 to HGF-induced motile response. HGF stimulates phosphorylation of PAK1 and PAK2. Knockdown of PAK1 inhibits HGF-stimulated migration and loss of cell-cell junctions in DU145 prostate carcinoma cells, whereas knockdown of PAK2 enhances loss of cell-cell junctions and increases lamellipodium extension but does not affect migration speed. On the other hand, in PC3 prostate carcinoma cells, which lack cell-cell junctions, knockdown of PAK1 or PAK2 reduces HGF-stimulated migration. PAK2 knockdown increases phosphorylation of PAKI, indicating that PAK2 provides a negative feedback on PAK1. We hypothesise that PAK2 acts in part via PAKI to regulate HGF-induced scattering.
机译:肝细胞生长因子(HGF)刺激上皮细胞解离(散射)和细胞迁移。 HGF诱导的散射需要几个Rho GTPases。 PAK1和PAK2是丝氨酸/苏氨酸激酶的p21激活激酶(PAK)家族的成员,并由Rho GTPases Rac和Cdc42激活。在这里,我们调查PAK1和PAK2对HGF诱导的运动反应的贡献。 HGF刺激PAK1和PAK2的磷酸化。敲低PAK1可抑制DU145前列腺癌细胞中HGF刺激的迁移和细胞-细胞连接的损失,而敲除PAK2可增强细胞-细胞连接的损失并增加lamellipodium延伸,但不影响迁移速度。另一方面,在缺乏细胞间连接的PC3前列腺癌细胞中,敲低PAK1或PAK2会降低HGF刺激的迁移。 PAK2敲低会增加PAKI的磷酸化,表明PAK2对PAK1提供了负反馈。我们假设PAK2部分通过PAKI来调节HGF诱导的散射。

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