STRUCTURE AND ROLE OF A TRANSFORMATION-SENSITIVE CELL SURFACE GLYCOPROTEIN

纤维连接蛋白是主要的细胞表面和细胞外基质 参与细胞粘附和迁移的糖蛋白。 合成 含关键纤维连接蛋白粘附识别肽 序列Gly-Arg-Gly-Asp-Ser静脉内给药 同时激发的小鼠的存活率显著提高 与黑色素瘤细胞进行实验性转移测定。 以来 发现肽的肾清除非常迅速， 正在测试肽衍生物与载体的缀合 作为增加其流通时间的手段。 此外 纤连蛋白与这个原始的肽识别序列相连接， 显示含有与其协同作用的第二结合位点， 产生充分的粘附亲和力和有效的跨膜效应 对细胞骨架组织的影响。 产生的突变体 定点诱变或缺失每个显示的位点 超过96%的活动损失，两种类型的 体外协同粘附和促进组织化的突变体 肌动蛋白微丝束。 对这一地区的研究可能会产生 一类新的纤连蛋白功能抑制剂。 另外两个细胞 粘附序列仅存在于某些纤连蛋白中 由于另一个结构域的mRNA选择性剪接而导致的分子。 除了黑色素瘤细胞，来自外周神经的胚胎细胞 发现系统使用这种细胞类型特异性结构域，其可以 只有来自神经细胞的细胞才能识别。 冠。 Gly-Arg-Gly-Asp-Ser肽及其类似物 抑制胚胎细胞在体节和心脏中的粘附 阵 然而，这种肽对节段性 板状细胞是体节的前体。 所述肽 基本上诱导细胞间聚集，这表明它 可以调节细胞-细胞粘附系统的表达。

Fibronectin is a major cell surface and extracellular matrix glycoprotein involved in cell adhesion and migration. A synthetic peptide containing the key fibronectin adhesive recognition sequence Gly-Arg-Gly-Asp-Ser administered intravenously substantially enhanced survival of mice challenged concurrently with melanoma cells in an experimental metastasis assay. Since renal clearance of the peptide was found to be very rapid, conjugation of a peptide derivative to a carrier is being tested as a means of increasing its time in the circulation. In addition to this original peptide recognition sequence, fibronectin was shown to contain a second binding site that synergizes with it to produce full adhesive affinity and efficient transmembrane effects of the peptide on cytoskeletal organization. Mutants produced by site-directed mutagenesis or deletion of each site displayed greater than 96 percent losses of activity, and the two types of mutants synergized in vitro for adhesion and promoting organization of actin microfilament bundles. Studies of this region may yield a novel class of inhibitor of fibronectin function. Two other cell adhesion sequences are present in only certain fibronectin molecules due to alternative mRNA splicing of another domain. Besides melanoma cells, embryonic cells from the peripheral nervous system were found to use this cell-type specific domain, which may be recognized only by cells derived originally from the neural crest. The Gly-Arg-Gly-Asp-Ser peptide and related analogues inhibited adhesion of embryonic cells involved in somite and heart formation. However, this peptide had unusual effects on segmental plate cells, which are the precursors of somites. The peptide substantially induced cell-to-cell aggregation, suggesting that it may regulate expression of a cell-cell adhesion system.