Endothelial cell-specific molecule 2 (ECSM2) localizes to cell-cell junctions and modulates bFGF-directed cell migration via the ERK-FAK pathway.
Endothelial cell-specific molecule 2 (ECSM2) localizes to cell-cell junctions and modulates bFGF-directed cell migration via the ERK-FAK pathway.
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DOI：
10.1371/journal.pone.0021482
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Shi C;Lu J;Wu W;Ma F;Georges J;Huang H;Balducci J;Chang Y;Huang Y
尽管在十年前通过计算机克隆首次发现了新的内皮细胞特异性基因，但内皮细胞特异性分子2（ECSM 2）的生物学功能直到最近才开始被理解。有限的数据表明其参与细胞迁移和凋亡。然而，ECSM2的潜在信号转导机制和新功能仍有待探索。产生兔抗ECSM 2单克隆抗体（RabMAb）并用于表征内源性ECSM 2蛋白。免疫印迹，免疫沉淀，去糖基化，免疫染色和共聚焦显微镜验证，内源性ECSM 2是一种质膜糖蛋白，优先表达于血管内皮细胞（EC）。异源表达和内源性ECSM 2的表达模式确定ECSM 2特别集中在细胞-细胞接触处。细胞聚集和transwell实验表明，ECSM2促进细胞间粘附和衰减碱性成纤维细胞生长因子（bFGF）驱动的EC迁移。通过ECSM2在EC中的过表达或敲低进行的功能获得或丧失测定表明，ECSM2通过FGF受体（FGFR）-细胞外调节激酶（ERK）-粘着斑激酶（FAK）途径调节bFGF指导的EC运动。FAK酪氨酸磷酸化（活化）和FAK的ERK依赖性丝氨酸磷酸化之间的平衡至关重要。提出了ECSM2信号如何影响bFGF/FGFR驱动的EC迁移的模型。ECSM 2可能是一种新的EC连接蛋白。它能促进细胞间粘附，抑制bFGF介导的细胞迁移。在机制上，ECSM2通过FGFR-ERK-FAK途径减弱EC运动性。研究结果表明，ECSM2可能是协调受体酪氨酸激酶（RTK），整合素和EC连接组分介导的信号传导的关键参与者，并可能在与内皮功能障碍和受损EC连接信号传导相关的疾病中具有重要意义。
Despite its first discovery by in silico cloning of novel endothelial cell-specific genes a decade ago, the biological functions of endothelial cell-specific molecule 2 (ECSM2) have only recently begun to be understood. Limited data suggest its involvement in cell migration and apoptosis. However, the underlying signaling mechanisms and novel functions of ECSM2 remain to be explored. A rabbit anti-ECSM2 monoclonal antibody (RabMAb) was generated and used to characterize the endogenous ECSM2 protein. Immunoblotting, immunoprecipitation, deglycosylation, immunostaining and confocal microscopy validated that endogenous ECSM2 is a plasma membrane glycoprotein preferentially expressed in vascular endothelial cells (ECs). Expression patterns of heterologously expressed and endogenous ECSM2 identified that ECSM2 was particularly concentrated at cell-cell contacts. Cell aggregation and transwell assays showed that ECSM2 promoted cell-cell adhesion and attenuated basic fibroblast growth factor (bFGF)-driven EC migration. Gain or loss of function assays by overexpression or knockdown of ECSM2 in ECs demonstrated that ECSM2 modulated bFGF-directed EC motility via the FGF receptor (FGFR)-extracellular regulated kinase (ERK)-focal adhesion kinase (FAK) pathway. The counterbalance between FAK tyrosine phosphorylation (activation) and ERK-dependent serine phosphorylation of FAK was critically involved. A model of how ECSM2 signals to impact bFGF/FGFR-driven EC migration was proposed. ECSM2 is likely a novel EC junctional protein. It can promote cell-cell adhesion and inhibit bFGF-mediated cell migration. Mechanistically, ECSM2 attenuates EC motility through the FGFR-ERK-FAK pathway. The findings suggest that ECSM2 could be a key player in coordinating receptor tyrosine kinase (RTK)-, integrin-, and EC junctional component-mediated signaling and may have important implications in disorders related to endothelial dysfunction and impaired EC junction signaling.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
8
作者：
Gan, Y.;Shi, C.;Huang, Y.
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Huang, Y.
影响因子：
3.3
作者：
Bryant, DM;Wylie, FG;Stow, JL
通讯作者：
Stow, JL
影响因子：
37.8
作者：
Brizzi, MF;Formato, L;Pegoraro, L
通讯作者：
Pegoraro, L