Glypican-6, a new member of the glypican family of cell surface heparan sulfate proteoglycans

The glypicans compose a family of glycosylphosphatidylinositol-anchored hep aran sulfate proteoglycans, Mutations in dally, a gene encoding a Drosophil a 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 gl ypican family have been identified in vertebrates, By sequencing expressed sequence tag clones and products of rapid amplifications of cDNA ends, we i dentified a sixth member of the glypican family. The glypican-6 mRNA encode s a protein of 555 amino acids that is most homologous to glypican-4 (ident ity of 63%). Expression of this protein in Namalwa cells shows a core prote in of similar to 60 kDa that is substituted with heparan sulfate only. GPC6 , the gene encoding human glypican-6, contains nine exons. Like GPC5, the g ene encoding glypican-5, GPC6 maps to chromosome 13q32,Clustering of the GP C5/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 s eries of gene and genome duplications. Based on similarities in sequence an d gene organization, glypican-1, glypican-2, glypican-1, and glypican-6 app ear to define a subfamily of glypicans, differing from the subfamily compri sing so far glypican-3 and glypican-5. Northern blottings indicate that gly pican-6 mRNA is widespread, with prominent expressions in human fetal kidne y and adult, ovary. In situ hybridization studies localize glypican-6 to me senchymal 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 presenc e of glypican-6 on the cell surface.