Booth B A, Boes M, Dake B L, Caldwell E E, Weiler J M, Bar R S
Diabetes and Endocrinology Research Center, The University of Iowa, Veterans Administration Medical Center, 3E19 VA, Iowa City, IA 52246, USA.
Growth Horm IGF Res. 2000 Aug;10(4):224-9. doi: 10.1054/ghir.2000.0158.
18 amino acid peptides from the C-terminal region of IGFBP-3, -5 (P3, P5), increased the incorporation of(35)SO(4)into proteoglycans in endothelial cells with greater stimulation in large vessel than microvessel cells. The homologous region of IGFBP-6 (P6) also stimulated sulfate uptake, but less potently than P3 and P5. P6 variants were synthesized with one or two amino acids changed to the basic amino acid in the equivalent position of P3. The P6 variants with one additional basic amino acid behaved similarly to P6. The P6 mutant with two altered amino acids was equipotent to P3. P3F, a scrambled version of P3 was less effective than P3. P3, P5, P6, P3F and all P6 variants all stimulated glucose uptake, which occurred only in microvessel cells. P1, P2, P4, and equimolar intact IGFBP-3 stimulated neither glucose uptake nor sulfate incorporation. Thus, C-terminal basic portions of IGFBP-3, -5 and -6 alter two specific functions of endothelial cells with sufficient differences to suggest mediation by distinct mechanisms.
来自胰岛素样生长因子结合蛋白-3（IGFBP-3）、-5（P3、P5）C末端区域的18个氨基酸肽，增加了内皮细胞中（35）SO（4）掺入蛋白聚糖的量，对大血管内皮细胞的刺激作用大于微血管内皮细胞。胰岛素样生长因子结合蛋白-6（P6）的同源区域也刺激了硫酸盐摄取，但效力低于P3和P5。合成了P6变体，其一个或两个氨基酸在P3的等效位置被替换为碱性氨基酸。额外含有一个碱性氨基酸的P6变体表现与P6相似。有两个氨基酸改变的P6突变体与P3等效。P3的乱序版本P3F的效果低于P3。P3、P5、P6、P3F和所有P6变体均刺激了葡萄糖摄取，且仅在微血管内皮细胞中发生。P1、P2、P4和等摩尔的完整IGFBP-3既不刺激葡萄糖摄取也不刺激硫酸盐掺入。因此，IGFBP-3、-5和-6的C末端碱性部分改变了内皮细胞的两种特定功能，差异足以表明是由不同机制介导的。
