Department of Dermatology, University of Rochester School of Medicine, Rochester, NY, USA.
Pigment Cell Melanoma Res. 2011 Feb;24(1):165-74. doi: 10.1111/j.1755-148X.2010.00797.x. Epub 2010 Nov 17.
Semaphorins are secreted and membrane bound proteins that regulate axon guidance through receptors Plexins and neuropilins. Plexin B1, the Semaphorin 4D receptor, is a recently described tumor suppressor protein for melanoma. We recently showed that Plexin B1 abrogates activation of the oncogenic receptor, c-Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. We have now investigated the effect of Plexin B1 on integrin-dependent pp125(FAK) activation, and the small GTP-binding protein Rho, in melanoma. Integrin receptors and Rho play critical roles in melanoma progression, through regulation of migration, proliferation and apoptosis. We engineered two human melanoma cell lines expressing Plexin B1 and analyzed integrin-dependent migration, integrin-dependent pp125(FAK) activation, and Rho activity. Results show that Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK). We also show that Rho activity is significantly reduced in cells expressing Plexin B1, and that Plexin B1 suppresses HGF-dependent Rho activation.
信号蛋白是分泌型和膜结合型蛋白，通过受体 Plexin 和神经丛蛋白来调节轴突导向。Plexin B1 是 Semaphorin 4D 的受体，是最近发现的黑色素瘤肿瘤抑制蛋白。我们最近表明，Plexin B1 通过其配体肝细胞生长因子 (HGF) 消除致癌受体 c-Met 的激活。我们现在研究了 Plexin B1 对黑色素瘤中整合素依赖性 pp125(FAK)激活和小 GTP 结合蛋白 Rho 的影响。整合素受体和 Rho 通过调节迁移、增殖和凋亡在黑色素瘤进展中发挥关键作用。我们构建了两种表达 Plexin B1 的人黑色素瘤细胞系，并分析了整合素依赖性迁移、整合素依赖性 pp125(FAK)激活和 Rho 活性。结果表明 Plexin B1 消除了整合素依赖性迁移和 pp125(FAK)的激活。我们还表明，表达 Plexin B1 的细胞中 Rho 活性显著降低，并且 Plexin B1 抑制了 HGF 依赖性 Rho 激活。
