Lee P D, Conover C A, Powell D R
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Proc Soc Exp Biol Med. 1993 Oct;204(1):4-29. doi: 10.3181/00379727-204-43630.
Insulin-like growth factor-binding protein (IGFBP)-1 is one of six homologous proteins that specifically bind and modulate the mitogenic and metabolic actions of insulin-like growth factor (IGF)-I and IGF-II. Of the six IGFBP, IGFBP-1 is the only one that displays rapid dynamic regulation in vivo, with serum levels varying 10-fold or more in relation to meals. The complementary cDNA for IGFBP-1 was first reported in 1988. The predicted 234-amino acid sequence has a molecular mass of 25.3 kDa. The N-terminal and C-terminal regions are highly homologous among rat, human, and bovine sequences, and contain 18 conserved cysteines which are postulated to provide a framework for ligand binding. The 65-residue midregion is less homologous and does not contain cysteines, but does include a Pro-Glu-Ser-Thr (PEST) domain that is typical of rapidly metabolized proteins. The gene for IGFBP-1 has been localized to human chromosome region 7p12-p14, where it is contiguous with the gene for IGFBP-3. IGFBP-1 mRNA and protein expression have been identified in human liver and uterine decidua, and in nonhuman kidney. In vitro and in vivo studies indicate that insulin is the primary regulator of IGFBP-1 expression in these tissues, and that the primary effect of insulin is rapid inhibition of transcription. On the other hand, cortisol, glucagon, and cAMP stimulate IGFBP-1 production. Limited data also show a potent stimulatory effect of phorbol esters. A detailed review of IGFBP-1 levels and physiology in vivo and in vitro is presented. The function of IGFBP-1 is not completely defined. However, several studies demonstrate that IGFBP-1 inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. Furthermore, IGFBP-1 regulation by insulin and glucoregulatory hormones in vitro and limited in vivo data are consistent with a role for IGFBP-1 in glucose counterregulation.
胰岛素样生长因子结合蛋白（IGFBP）-1是六种同源蛋白之一，它能特异性结合并调节胰岛素样生长因子（IGF）-I和IGF-II的促有丝分裂及代谢作用。在这六种IGFBP中，IGFBP-1是唯一一种在体内表现出快速动态调节的蛋白，其血清水平会因进食而变化10倍或更多。IGFBP-1的互补cDNA于1988年首次报道。预测的234个氨基酸序列的分子量为25.3 kDa。大鼠、人类和牛的序列中，N端和C端区域高度同源，且含有18个保守的半胱氨酸，推测这些半胱氨酸为配体结合提供了框架。65个残基的中间区域同源性较低，不含半胱氨酸，但包含一个典型的快速代谢蛋白的脯氨酸-谷氨酸-丝氨酸-苏氨酸（PEST）结构域。IGFBP-1基因已定位到人类染色体区域7p12 - p14，与IGFBP-3基因相邻。在人类肝脏、子宫蜕膜以及非人类肾脏中已鉴定出IGFBP-1 mRNA和蛋白表达。体外和体内研究表明，胰岛素是这些组织中IGFBP-1表达的主要调节因子，胰岛素的主要作用是快速抑制转录。另一方面，皮质醇、胰高血糖素和cAMP会刺激IGFBP-1的产生。有限的数据还显示佛波酯有强大的刺激作用。本文对体内外IGFBP-1水平及生理学进行了详细综述。IGFBP-1的功能尚未完全明确。然而，多项研究表明，IGFBP-1可抑制IGF与细胞表面受体的结合，从而抑制IGF介导的促有丝分裂和细胞代谢作用。此外，体外胰岛素和糖调节激素对IGFBP-1的调节以及有限的体内数据表明，IGFBP-1在葡萄糖反向调节中发挥作用。
