國家衛生研究院 NHRI:Item 3990099045/7482
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    題名: Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration
    作者: Chen, CH;Ho, YC;Ho, HH;Chang, IC;Kirsch, KH;Chuang, YJ;Layne, MD;Yet, SF
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: AIMS: Cysteine-rich protein (CRP) 2, a member of the LIM-only CRP family that contains two LIM domains, is expressed in vascular smooth muscle cells (VSMCs) of blood vessels and functions to repress VSMC migration and vascular remodeling. The goal of this study was to define the molecular mechanisms by which CRP2 regulates VSMC migration. METHODS AND RESULTS: Transfection of VSMCs with CRP2-EGFP constructs revealed that CRP2 associated with the actin cytoskeleton. In response to chemoattractant stimulation, Csrp2 (mouse CRP2 gene symbol)-deficient (Csrp2-/-) VSMCs exhibited increased lamellipodia formation. Re-introduction of CRP2 abrogated the enhanced lamellipodia formation and migration of Csrp2-/- VSMCs following chemoattractant stimulation. Mammalian 2-hybrid and coimmunoprecipitation assays demonstrated that CRP2 interacts with p130Cas, a scaffold protein important for lamellipodia formation and cell motility. Immunofluorescence staining showed that CRP2 colocalized with phospho-p130Cas at focal adhesions (FAs)/terminal ends of stress fibers in non-migrating cells. Interestingly, in migrating cells phospho-p130Cas localized to the leading edge of lamellipodia and FAs while CRP2 was restricted to FAs and stress fibers. Furthermore, we demonstrated that p130Cas expression and phosphorylation promote neointima formation following arterial injury. CONCLUSION: These studies demonstrate that CRP2 sequesters p130Cas at FAs, thereby reducing lamellipodia formation and blunting VSMC migration.
    日期: 2013-12
    關聯: Cardiovascular Research. 2013 Dec;100(3):461-471.
    Link to: http://dx.doi.org/10.1093/cvr/cvt207
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-6363&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000327398400015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84887944174
    顯示於類別:[林秀芳] 期刊論文

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