Veugelers M, De Cat B, Ceulemans H, Bruystens A M, Coomans C, Dürr J, Vermeesch J, Marynen P, David G
Laboratory for Glycobiology, Center for Human Genetics, University of Leuven, B-3000, Belgium.
J Biol Chem. 1999 Sep 17;274(38):26968-77. doi: 10.1074/jbc.274.38.26968.
The glypicans compose a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans. Mutations in dally, a gene encoding a Drosophila glypican, and in GPC3, the gene for human glypican-3, implicate glypicans in the control of cell growth and division. So far, five members of the glypican family have been identified in vertebrates. By sequencing expressed sequence tag clones and products of rapid amplifications of cDNA ends, we identified a sixth member of the glypican family. The glypican-6 mRNA encodes a protein of 555 amino acids that is most homologous to glypican-4 (identity of 63%). Expression of this protein in Namalwa cells shows a core protein of approximately 60 kDa that is substituted with heparan sulfate only. GPC6, the gene encoding human glypican-6, contains nine exons. Like GPC5, the gene encoding glypican-5, GPC6 maps to chromosome 13q32. Clustering of the GPC5/GPC6 genes on chromosome 13q32 is strongly reminiscent of the clustering of the GPC3/GPC4 genes on chromosome Xq26 and suggests GPCs arose from a series of gene and genome duplications. Based on similarities in sequence and gene organization, glypican-1, glypican-2, glypican-4, and glypican-6 appear to define a subfamily of glypicans, differing from the subfamily comprising so far glypican-3 and glypican-5. Northern blottings indicate that glypican-6 mRNA is widespread, with prominent expressions in human fetal kidney and adult ovary. In situ hybridization studies localize glypican-6 to mesenchymal tissues in the developing mouse embryo. High expressions occur in smooth muscle cells lining the aorta and other major blood vessels and in mesenchymal cells of the intestine, kidney, lung, tooth, and gonad. Growth factor signaling in these tissues might in part be regulated by the presence of glypican-6 on the cell surface.
磷脂酰肌醇蛋白聚糖构成了一个糖基磷脂酰肌醇锚定的硫酸乙酰肝素蛋白聚糖家族。果蝇磷脂酰肌醇蛋白聚糖编码基因dally以及人类磷脂酰肌醇蛋白聚糖-3基因GPC3中的突变表明，磷脂酰肌醇蛋白聚糖参与细胞生长和分裂的调控。到目前为止，已在脊椎动物中鉴定出磷脂酰肌醇蛋白聚糖家族的五个成员。通过对表达序列标签克隆和cDNA末端快速扩增产物进行测序，我们鉴定出了磷脂酰肌醇蛋白聚糖家族的第六个成员。磷脂酰肌醇蛋白聚糖-6 mRNA编码一种由555个氨基酸组成的蛋白质，该蛋白质与磷脂酰肌醇蛋白聚糖-4的同源性最高（同一性为63%）。此蛋白在Namalwa细胞中的表达显示出一个约60 kDa的核心蛋白，该核心蛋白仅被硫酸乙酰肝素取代。编码人类磷脂酰肌醇蛋白聚糖-6的基因GPC6包含9个外显子。与编码磷脂酰肌醇蛋白聚糖-5的基因GPC5一样，GPC6定位于13号染色体q32区。13号染色体q32区的GPC5/GPC6基因成簇现象强烈让人联想到X染色体q26区的GPC3/GPC4基因成簇现象，这表明磷脂酰肌醇蛋白聚糖是由一系列基因和基因组重复产生的。基于序列和基因组织的相似性，磷脂酰肌醇蛋白聚糖-1、磷脂酰肌醇蛋白聚糖-2、磷脂酰肌醇蛋白聚糖-4和磷脂酰肌醇蛋白聚糖-6似乎定义了一个磷脂酰肌醇蛋白聚糖亚家族，不同于目前由磷脂酰肌醇蛋白聚糖-3和磷脂酰肌醇蛋白聚糖-5组成的亚家族。Northern印迹分析表明，磷脂酰肌醇蛋白聚糖-6 mRNA广泛分布，在人类胎儿肾脏和成年卵巢中表达显著。原位杂交研究将磷脂酰肌醇蛋白聚糖-6定位于发育中的小鼠胚胎的间充质组织。在主动脉和其他主要血管的平滑肌细胞以及肠道、肾脏、肺、牙齿和性腺的间充质细胞中高表达。这些组织中的生长因子信号传导可能部分受细胞表面磷脂酰肌醇蛋白聚糖-6的存在调控。
