PURIFICATION AND CHARACTERIZATION OF A NATURALLY-OCCURRING VASCULAR ENDOTHELIAL GROWTH-FACTOR PLACENTA GROWTH-FACTOR HETERODIMER

PURIFICATION AND CHARACTERIZATION OF A NATURALLY-OCCURRING VASCULAR ENDOTHELIAL GROWTH-FACTOR PLACENTA GROWTH-FACTOR HETERODIMER
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DOI:
10.1074/jbc.270.13.7717
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发表时间:
1995-03-31
影响因子:
4.8
通讯作者:
THOMAS, KA
THOMAS, KA
中科院分区:
生物学2区
文献类型:
--
作者:
DISALVO, J;BAYNE, ML;THOMAS, KA

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血管内皮生长因子(VEGF)是一种高效的、选择性的内皮细胞有丝分裂原,在体内是血管生成的,在低氧诱导下,一种同源蛋白胎盘生长因子(PlGF)也被报道对培养的内皮细胞具有促有丝分裂作用。大鼠GS-SL胶质瘤细胞株不仅产生VEGF同源二聚体,还产生PlGF同源二聚体和一种由VEGF和PlGF亚基组成的新的异源二聚体,将这三种二聚体纯化为表观均一,并比较它们的结构和促分裂活性。PlGF异源二聚体是血管内皮细胞的有丝分裂原,其活性与血管内皮生长因子同源二聚体几乎相同,因此,血管内皮生长因子同源二聚体的某些生物学活性可能是由血管内皮生长因子介导的。PlGF异源二聚体。相反,纯的PlGF同源二聚体只有在较高的,可能是非生理性的浓度下才对内皮细胞具有促有丝分裂作用;因此,它们的促有丝分裂活性与这些细胞的生物学相关性并不明显,然而,不仅同源二聚体的存在,而且异源二聚体的存在明显扩大了血管内皮生长因子/PlGF和同源血小板衍生生长因子系统之间的相似性。
Vascular endothelial growth factor (VEGF) is a potent and selective mitogen for endothelial cells that is angiogenic in vivo and induced by hypoxia, A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture, The rat GS-SL glioma cell line produces not only VEGF homodimers but also PlGF homodimers and a novel heterodimer composed of VEGF and PlGF subunits, All three dimeric forms were purified to apparent homogeneity, and their structures and mitogenic activities were compared, VEGF . PlGF heterodimers are vascular endothelial cell mitogens nearly as potent as VEGF homodimers, Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF . PlGF heterodimers. In contrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious, However, the existence of not only homodimers but also heterodimers clearly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.