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激活红细胞生成素产生肝细胞受体 A2 通过去磷酸化粘着斑激酶减轻人输卵管上皮细胞的黏附。

Activation of erythropoietin-producing hepatocellular receptor A2 attenuates cell adhesion of human fallopian tube epithelial cells via focal adhesion kinase dephosphorylation.

机构信息

Institute of Reproductive Immunology, College of Life Science and Technology, Jinan University, Guangzhou City, People's Republic of China.

出版信息

Mol Cell Biochem. 2012 Feb;361(1-2):259-65. doi: 10.1007/s11010-011-1111-z. Epub 2011 Oct 19.

DOI:10.1007/s11010-011-1111-z
PMID:22009484
Abstract

Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) and its predominant ligand EphrinA1 have been studied extensively for their roles of mediating cell adhesion in epithelial cells. However, EphA2 signaling in human fallopian tube epithelial cells is poorly understood. In this study, primary cultured fallopian tube epithelial cells were used as a model treated with EphrinA1-Fc or IgG-Fc (control), to explore the role of EphA2 signal and its network involved in the regulation of cell adhesion of tubal epithelia cells. The activation of EphA2 and focal adhesion kinase (FAK) was evaluated by western blotting assay in the cultured fallopian tube epithelia cells, of which the cell adhesion activity was determined by MTT assay. A significantly negative correlation was found between phosphorylated-EphA2 (Pho-EphA2) and phosphorylated-FAK (Pho-FAK) after exposure to EphrinA1-Fc (P = 0.000; r = -0.848). EphrinA1-Fc increased Pho-EphA2 and reduced Pho-FAK in seconds, with the apex level of Pho-EphA2 and the nadir level of Pho-FAK detected at the same time (10 min). Cell adhesion of the cultured cells supplemented with EphrinA1-Fc appeared to be weaker than that of the controls at the later time points of the treatment (from 30 to 120 min) (P < 0.05). Taken together, the EphrinA1 addition directly induces an elevated Pho-EphA2 accompanied by a decreased Pho-FAK in human fallopian tube epithelia cells. Furthermore, activation of EphA2 participates in the regulation of fallopian tube cell adhesion via FAK dephosphorylation.

摘要

酪氨酸激酶受体促红细胞生成素产生肝细胞受体 A2(EphA2)及其主要配体 EphrinA1 在介导上皮细胞黏附中的作用已得到广泛研究。然而,EphA2 信号在人输卵管上皮细胞中的作用知之甚少。在这项研究中,使用原代培养的输卵管上皮细胞作为模型,用 EphrinA1-Fc 或 IgG-Fc(对照)处理,以探讨 EphA2 信号及其网络在调节输卵管上皮细胞黏附中的作用。通过 Western blot 检测培养的输卵管上皮细胞中 EphA2 和粘着斑激酶(FAK)的激活,通过 MTT 测定法测定细胞黏附活性。 EphrinA1-Fc 处理后,发现磷酸化-EphA2(Pho-EphA2)与磷酸化-FAK(Pho-FAK)之间呈显著负相关(P=0.000;r=-0.848)。 EphrinA1-Fc 在几秒钟内增加 Pho-EphA2 并减少 Pho-FAK,同时检测到 Pho-EphA2 的峰值和 Pho-FAK 的最低点(10 分钟)。补充 EphrinA1-Fc 的培养细胞的黏附作用似乎在处理后的较晚时间点(从 30 分钟到 120 分钟)比对照组弱(P<0.05)。总之,EphrinA1 的添加直接诱导人输卵管上皮细胞中 EphA2 的磷酸化升高,同时 FAK 的磷酸化降低。此外,EphA2 的激活通过 FAK 去磷酸化参与调节输卵管细胞黏附。

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Reprod Biol Endocrinol. 2018 Sep 3;16(1):84. doi: 10.1186/s12958-018-0403-5.

本文引用的文献

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Meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors.多个微阵列数据集的荟萃分析揭示了实体瘤转移的共同基因特征。
BMC Med Genomics. 2011 Jul 7;4:56. doi: 10.1186/1755-8794-4-56.
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Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy.细胞皮层蛋白和粘着斑激酶作为喉癌前病变患者癌症风险的预测因子。
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Focal adhesions are sites of integrin extension.
粘着斑是整合素延伸的部位。
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Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins.粘着斑的解体需要网格蛋白依赖的整合素内吞作用。
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PP2 regulates human trophoblast cells differentiation by activating p38 and ERK1/2 and inhibiting FAK activation.PP2通过激活p38和ERK1/2并抑制粘着斑激酶(FAK)的激活来调节人滋养层细胞的分化。
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Binding of soluble fibronectin to integrin alpha5 beta1 - link to focal adhesion redistribution and contractile shape.可溶性纤连蛋白与整联蛋白α5β1的结合——与粘着斑重新分布和收缩性形态的关联
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