HISTIDINE-RICH GLYCOPROTEIN: CELLULAR AND MOLECULAR BIOL

富含组氨酸的糖蛋白(HRGP)是一种多功能蛋白质，是一种 在血浆和血小板中发现。它与纤溶酶原特异地相互作用， 肝素和凝血酶原蛋白，这表明它可能在 调节纤溶和调节抗凝活性 肝素。这个项目的总体目标是研究细胞 HRGP的生物学、生物化学和分子生物学。初步数据 显示了HRGP与纤维蛋白原的新的特异性相互作用 证明了HRGP被特异性地掺入纤维蛋白凝块。这个 HRGP-纤维蛋白原/纤维蛋白相互作用对纤维蛋白的功能作用(S) 聚合以及对纤维蛋白凝胶结构的影响 学习。HRGP-纤维蛋白原/纤维蛋白原相互作用是否在 介导HRGP与凝血酶激活的血小板和小鼠腹膜的结合 将对巨噬细胞进行研究。这些新的HRGP的细胞生物学 肝素与细胞表面和细胞表面的相互作用 我们将研究血小板与巨噬细胞的相互作用。详细分析了 HRGP的结构与功能的关系是进一步研究HRGP的关键 阐明这种分子的生物学，将由两个人进行 接近了。HRGP的单独功能配基结合域将是 以酶促产生的HRGP片段的分离为特征 消化和化学碎片。HRGP分子的详细图谱 将通过产生具有反应性的抗HRGP单克隆来建立 针对HRGP的特定配体结合域。HRGP基因将 通过免疫化学方法筛选人肝cDNA库分离得到 通过人工合成的寡核苷酸建立HRGP的一级序列 并检测HRGP的结构和表达调控 基因(S)。细胞内HRGP受体及其结合域的研究 将使用单抗独特型来研究各种配体。 抗受体抗体。这些研究将提供重要的见解 探讨HRGP的生物学及止血和止血的分子机制 血栓形成。

Histidine-rich glycoprotein (HRGP) is a multifunctional protein that is found in plasma and platelets. It specifically interacts with plasminogen, heparin, and thrombospondin, suggesting that it may be important in modulating fibrinolysis and regulating the anticoagulant activity of heparin. The overall objective of this project is to study the cell biology, biochemistry, and molecular biology of HRGP. Preliminary data have shown a new specific interaction of HRGP with fibrinogen and demonstrated specific incorporation of HRGP into fibrin clots. The functional role(s) of the HRGP-fibrinogen/fibrin interactions on fibrin polymerization as well as on the structure of the fibrin gel will be studied. Whether the HRGP-fibrinogen/fibrin interactions play a role in mediating HRGP binding to thrombin-activated platelets and mouse peritoneal macrophages will be investigated. The cell biology of these new HRGP interactions relating to heparin binding to cell surfaces and platelet-macrophage interactions will be studied. A detailed analysis of the structure-function relationships of HRGP is crucial for the further elucidation of the biology of this molecule and will be carried out by two approaches. The separate functional ligand-binding domains of HRGP will be characterized by isolation of HRGP fragments generated by enzymatic digestion and chemical fragmentation. A detailed map of the HRGP molecule will be established by generating anti-HRGP monoclonals with reactivity directed against specific ligand-binding domains of HRGP. HRGP cDNA will be isolated by screening a human liver cDNA library both immunochemically and by synthetic oligonucleotides to establish the primary sequence of HRGP and to examine the structure and regulation of expression of the HRGP gene(s). The cellular HRGP receptors and the HRGP-binding domains on the various ligands will be studied using monoclonal anti-idiotypic anti-receptor antibodies. These studies will provide important insights into the biology of HRGP and the molecular mechanisms of hemostasis and thrombosis.