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J Biol Chem, Vol. 274, Issue 38, 26968-26977, September 17, 1999
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From the 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 ~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.
Laboratory for Glycobiology and
Developmental Genetics, ¶ Laboratory for Human Genome Analysis,
Center for Human Genetics, University of Leuven and Flanders
Interuniversity Institute for Biotechnology,
Leuven B-3000, Belgium
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