A COMPARISON OF THE BIOLOGICAL-ACTIVITY OF THE RECOMBINANT INTACT AND TRUNCATED INSULIN-LIKE GROWTH FACTOR-I (IGF-1)
A COMPARISON OF THE BIOLOGICAL-ACTIVITY OF THE RECOMBINANT INTACT AND TRUNCATED INSULIN-LIKE GROWTH FACTOR-I (IGF-1)
复制标题
DOI：
10.1016/0167-4889(89)90209-7
复制
发表时间：
1989-05-10
期刊：
影响因子：
--
通讯作者：
SARA, VR
中科院分区：
文献类型：
--
作者：
CARLSSONSKWIRUT, C;LAKE, M;SARA, VR
从人胎儿和成人脑中分离到一种缺失氨基端三肽Gly-Pro-Glu的胰岛素样生长因子1（IGF-1）截短型。这种截短的IGF-1显示出比从人血清中分离的IGF-1更强的交叉反应性和对脑细胞的生物学作用。我们现在提出的数据上的重组DNA衍生的截短的IGF-1缺乏氨基末端三肽。重组截短的IGF-1在从人胎儿和成人脑和胎盘膜中置换[125 I]IGF-1方面比重组和天然IGF-1强1.4-5倍。当使用截短的IGF-1作为放射性配体时，这些差异略有增强。与胰岛素样生长因子2（IGF-2）相比，从大鼠肝膜置换[125 I]IGF-2的相对效价为重组截短型IGF-1，0.3%和重组IGF-1，0.2%。与重组IGF-1相比，重组截短的IGF-1对从人羊水中分离的低分子量结合蛋白（IGF-BP）的亲和力降低了100倍。同样，IGF-BP抑制重组截短型IGF-1受体结合的效力比重组IGF-1低100倍。重组截短型IGF-1在刺激胎鼠脑细胞DNA合成方面的效力是重组和天然IGF-1的4倍。重组截短的IGF-1的这种生物活性不受IGF-BP的影响，IGF-BP的浓度消除了重组IGF-1的生物活性。提出了IGF-BP结合的完整IGF-1代表IGF-1的内分泌形式，而截短的IGF-1代表IGF-1的旁分泌或自分泌形式的假设。
A truncated form of insulin-like growth factor 1 (IGF-1), which lacked the aminoterminal tripeptide Gly-Pro-Glu, has been isolated from human fetal and adult brian. This truncated IGF-1 displayed more potent cross-reactivity and biological action on brain cells than IGF-1 isolated from human serum. We now present data on a recombinant DNA-derived truncated IGF-1 lacking the aminoterminal tripeptide. Recombinant truncated IGF-1 was 1.4-5-times more potent than recombinant and natural IGF-1 in displacing [125I]IGF-1 from human fetal and adult brain and placenta membranes. These differences were slightly enhanced when truncated IGF-1 was used as radioligand. The relative potencies compared to insulin-like growth factor 2 (IGF-2) in displacing [125I]IGF-2 from rat liver membranes were recombinant truncated IGF-1, 0.3% and recombinant IGF-1, 0.2%. Recombinant truncated IGF-1 displayed 100-fold reduced affinity for the low molecular weight binding protein (IGF-BP) isolated from human amniotic fluid when compared to recombinant IGF-1. Likewise, the IGF-BP was 100-fold less potent in inhibiting the receptor binding of recombinant truncated IGF-1 than that of recombinant IGF-1. Recombinant truncated IGF-1 was 4-times more potent than recombinant and natural IGF-1 in stimulating DNA synthesis in fetal rat brain cells. This biological activity of recombinant truncated IGF-1 was not affected by the IGF-BP at concentrations which abolished the biological activity of recombinant IGF-1. The hypothesis that IGF-BP bound intact IGF-1 represents the endocrine form of IGF-1, whereas truncated IGF-1 represents the paracrine or autocrine form of IGF-1, is proposed.