Glycosylation is essential for efficient secretion but not for permeability-enhancing activity of vascular permeability factor (vascular endothelial growth factor).

Glycosylation is essential for efficient secretion but not for permeability-enhancing activity of vascular permeability factor (vascular endothelial growth factor).
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糖基化对于有效分泌至关重要,但对于血管通透性因子(血管内皮生长因子)的通透性增强活性却不是必需的。

DOI:
10.1016/0006-291x(91)91752-x
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发表时间:
1991
影响因子:
3.1
通讯作者:
Yeo,KT
Yeo,KT
中科院分区:
生物学4区
文献类型:
--
作者:
Yeo,TK;Senger,DR;Dvorak,HF;Freter,L;Yeo,KT

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供应实体瘤的微血管系统的高渗透性主要归因于异二聚体Mr 34,000- 43,000肿瘤分泌蛋白,血管渗透性因子。在还原后,由第10系肿瘤细胞分泌的血管渗透性因子通过SDS-PAGE分离成Mr 24,000、19,500和15,000的3个离散条带。我们在这里证明,线10血管通透性因子是一个N-连接的糖蛋白。非糖基化血管通透性因子在还原性SDS-PAGE上迁移为Mr 20,000和15,000的两条带。脉冲追踪研究表明,所有三条链的天然血管通透性因子分泌迅速合成后,以相等的速度,与细胞的半保留时间为1.37分钟。当糖基化被衣霉素阻止,个别乐队的非糖基化血管通透性因子也分泌以相等的速度,但更慢(1.60分钟)比天然糖蛋白。糖基化和非糖基化形式的血管通透性因子在增加真皮血管通透性方面同样有效。
The hyperpermeability of the microvasculature supplying solid tumors is largely attributable to a heterodimeric Mr34,000–43,000 tumor-secreted protein, vascular permeability factor. Upon reduction, the vascular permeability factor secreted by line 10 tumor cells is resolved by SDS-PAGE into 3 discrete bands of Mr24,000, 19,500, and 15,000. We demonstrate here that line 10 vascular permeability factor is an N-linked glycoprotein. Nonglycosylated vascular permeability factor migrates on reduced SDS-PAGE as two bands of Mr20,000 and 15,000. Pulse-chase studies demonstrated that all three chains of native vascular permeability factor were secreted rapidly following synthesis and at equal rates, with a cellular half-retention time of ∼37 min. When glycosylation was prevented by tunicamycin, individual bands of nonglycosylated vascular permeability factor were also secreted at equivalent rates, but much more slowly (∼60 min) than native glycoprotein. Both glycosylated and nonglycosylated forms of vascular permeability factor were equally potent at increasing dermal vessel permeability.