کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9902319 | 1545799 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Novel highly efficient intrabody mediates complete inhibition of cell surface expression of the human vascular endothelial growth factor receptor-2 (VEGFR-2/KDR)
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کلمات کلیدی
FACSmAbscFvHRPHUVECSKDRMonoclonal antibody - آنتی بادی مونوکلونالIntracellular immunization - ایمن سازی داخل سلولیporcine aortic endothelial cells - سلول های اندوتلیال آئورت گوشت خوکHuman umbilical vein endothelial cells - سلول های اندوتلیالی ورید ناف انسانendoplasmatic reticulum - سلولهای اندوپلاسمیVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)fluorescence-activated cell sorter - فلورسانس فعال سلول مرتب سازHorseradish peroxidase - پراکسیداز هوررادیشkinase insert domain-containing receptor - کیناز گیرنده حاوی دامنه را وارد کنید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوتکنولوژی یا زیستفناوری
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چکیده انگلیسی
The human vascular endothelial growth factor receptor-2 (VEGFR-2/KDR) and its ligand vascular endothelial growth factor (VEGF) play an essential role in tumor angiogenesis and in haematological malignancies. To inhibit VEGF induced signalling, intrabodies derived from two scFv fragments recognizing the VEGF receptor were generated. When these intrabodies were expressed in endothelial cells, they blocked the transport of KDR to the cell surface. We developed a cell culture model using porcine aortic endothelial cells overexpressing KDR for testing the efficiency of anti-KDR intrabodies. The two intrabodies were targeted to the ER and colocalised with the KDR receptor in an intracellular compartment. No degradation of the receptor was observed. An immature incomplete glycosylated protein of 195 kDa was detected, suggesting that the intrabodies affect the maturation of the receptor. Despite the presence of significant amounts of receptor protein, the inactivation by one of the two intrabodies was highly effective, resulting in complete functional inhibition of KDR and inhibition of in vitro angiogenesis. The new intrabody appears to be a powerful tool with which to inhibit KDR function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Immunological Methods - Volume 300, Issues 1â2, May 2005, Pages 146-159
Journal: Journal of Immunological Methods - Volume 300, Issues 1â2, May 2005, Pages 146-159
نویسندگان
Thomas Böldicke, Holger Weber, Peter P. Mueller, Bernhard Barleon, Maria Bernal,