Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor
Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor
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DOI：
10.1042/bj3160703
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发表时间：
1996-06-15
影响因子：
4.1
通讯作者：
McCarthy, JEG
中科院分区：
文献类型：
--
作者：
Birkenhager, R;Schneppe, B;McCarthy, JEG
血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）是具有血管生成特性的二聚体生长因子家族的成员。VEGF是一种高效特异的内皮细胞有丝分裂原，在体内血管生成中发挥重要作用。PIGF的作用不太清楚。我们使用pCYTEXP表达系统在大肠杆菌中表达单体剪接形式VEGF-165、VEGF-121、PIGF-1和PIGF-2作为未融合基因。体外二聚化实验表明，同源和异源二聚体可以形成这些单体蛋白质。测试了二聚体在体内促进毛细血管生长和刺激培养的人血管内皮细胞中DNA合成的能力。包含不同VEGF剪接形式或VEGF/PlGF剪接形式的组合的异源二聚体显示出促有丝分裂活性。结果表明，四种不同的异源二聚体生长因子可能具有尚未表征的体内功能。
Vascular endothilial growth factor (VEGF) and placenta growth factor (PIGF) are members of a dimeric-growth-factor family with angiogenic properties. VEGF is a highly potent and specific mitogen for endothelial cells, playing a vital role in angiogenesis in vivo. The role of PIGF is less clear. We expressed the monomeric splice forms VEGF-165, VEGF-121, PIGF-1 and PIGF-2 as unfused genes in Escherichia coli using the pCYTEXP expression system. In vitro dimerization experiments revealed that both homo- and hetero-dimers can be formed from these monomeric proteins. The dimers were tested for their ability to promote capillary growth in vivo and stimulate DNA synthesis in cultured human vascular endothelial cells. Heterodimers comprising different VEGF splice forms, or combinations of VEGF/PIGF splice forms, showed mitogenic activity. The results demonstrate that four different heterodimeric growth factors are likely to have as yet uncharacterized functions in vivo.