The integrin alpha5beta1 regulates alphavbeta3-mediated extracellular signal-regulated kinase activation.
The integrin alpha5beta1 regulates alphavbeta3-mediated extracellular signal-regulated kinase activation.
复制标题
整合素 alpha5beta1 调节 alphavbeta3 介导的细胞外信号调节激酶激活。
DOI：
10.1016/j.jss.2004.08.015
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Corbett,SiobhanA
中科院分区：
文献类型：
--
作者：
Ly,DaphneP;Corbett,SiobhanA
背景整合素介导的细胞迁移对于伤口修复至关重要。先前的研究表明，整合素与细胞外基质（ECM）之间的相互作用可以启动细胞内信号通路来调节细胞运动。粘着斑激酶 (FAK) 和细胞外信号调节激酶/激活的丝裂原激活蛋白激酶 (ERK/MAPK) 信号通路都是有效细胞迁移所必需的。我们之前的工作表明，整合素α5β1的共表达抑制αvβ3介导的细胞迁移。我们假设α5β1可能通过调节这些αvβ3介导的细胞内信号传导事件来调节细胞迁移。方法通过流式细胞术监测B3（αvβ3+）和B3C5（αvβ3+/α5β1+）细胞以确定整合素表达。允许细胞在纤维蛋白原 (FBG) 包被的 Transwell 上迁移，无论有或没有 PD98059（ERK 激活剂、丝裂原激活蛋白激酶激酶 (MEK) 的抑制剂）。使用固定、染色和细胞计数来量化细胞迁移。裂解粘附于 FBG 的细胞，并通过免疫印迹和图像分析光密度测定来分析 FAK 和 ERK/MAPK 激活。所有实验均重复三次。 结果 PD98059 处理显着降低了 FBG 上 αvβ3 介导的细胞迁移 (P = 0.0001)，达到与未处理的 B3C5 细胞相当的水平。与 B3C5 细胞相比，粘附 FBG 后，B3 细胞的 ERK/MAPK 激活显着增加。然而，在 FAK 激活方面没有检测到显着差异。 结论 通过 ERK/MAPK 途径的信号传导是 αvβ3 介导的 FBG 上有效迁移所必需的。整合素 α5β1 对 αvβ3 介导的迁移的抑制与响应粘附的 ERK/MAPK 激活强度和持续时间的改变相关，但与 FAK 激活无关。这表明α5β1对αvβ3介导的细胞迁移的调节作用的机制。
BACKGROUNDIntegrin-mediated cell migration is essential for wound repair. Previous studies have shown that the interaction between integrins and the extracellular matrix (ECM) can initiate intracellular signaling pathways to regulate cell movement. Both the focal adhesion kinase (FAK) and the extracellular signal-regulated kinase/activated mitogen-activated protein kinase (ERK/MAPK) signaling pathways are required for efficient cell migration. Our previous work has shown that co-expression of the integrin α5β1 inhibits αvβ3-mediated cell migration. We hypothesized that α5β1 may regulate cell migration by modulating these αvβ3-mediated intracellular signaling events.METHODSCHO B3 (αvβ3+) and B3C5 (αvβ3+/α5β1+) cells were monitored by flow cytometry to determine integrin expression. Cells were allowed to migrate on fibrinogen (FBG)-coated transwells, with or without PD98059, an inhibitor of the ERK activator, mitogen-activated protein kinase kinase (MEK). Fixation, staining, and cell counting were used to quantify cell migration. Cells adherent to FBG were lysed and analyzed for FAK and ERK/MAPK activation by immunoblotting followed by image analysis densitometry. All experiments were repeated in triplicate.RESULTSTreatment with PD98059 significantly decreased αvβ3-mediated cell migration on FBG (P = 0.0001) to a level comparable to untreated B3C5 cells. Following adhesion to FBG, B3 cells demonstrated a marked increase in ERK/MAPK activation compared to B3C5 cells. However, no significant difference was detected in FAK activation.CONCLUSIONSignaling through the ERK/MAPK pathway is required for efficient αvβ3-mediated migration on FBG. Inhibition of αvβ3-mediated migration by the integrin α5β1 correlates with altered intensity and duration of ERK/MAPK activation, but not FAK activation, in response to adhesion. This suggests a mechanism for the regulatory effect of α5β1 on αvβ3-mediated cell migration.
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