Glypican

The glypican family of Heparan Sulfate proteoglycans are anchored to the cell-surface via a covalent linkage to glycosylphosphatidylinositol (GPI). Six glypican family members have been identified in vertebrates, two in "Drosophila" and one in "C. elegans". [cite journal | author = Filmus, J. | title = Glypicans in growth control and cancer | journal = Glycobiology | year=2001 | volume=11 | issue=3 | pages=19R–23R | pmid = 11320054 | doi = 10.1093/glycob/11.3.19R]

Glypicans can modify cell signaling pathways and contribute to cellular proliferation and tissue growth. In "Drosophila", the glypican "dally" assists diffusion of the BMP-family growth-promoting morphogen Decapentaplegic in the developing wing, while the developing haltere lacks "dally" and remains small.cite journal | author = Crickmore MA, Mann RS | title = Hox control of morphogen mobility and organ development through regulation of glypican expression | journal = Development | volume = 134 | issue = 2 | pages = 327–34 | year = 2007 | month = January | pmid = 17166918 | doi = 10.1242/dev.02737 | url = | issn = ] Extracellular localization of the other glypican in "Drosophila", "dally-like", is also required for the proper level of Hedgehog signaling in the developing wing.cite journal | author = Gallet A, Staccini-Lavenant L, Thérond PP | title = Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis | journal = Dev. Cell | volume = 14 | issue = 5 | pages = 712–25 | year = 2008 | month = May | pmid = 18477454 | doi = 10.1016/j.devcel.2008.03.001 | url = | issn = ]

In humans, glypican-1 is overexpressed in breastcite journal | author = Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M | title = Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells | journal = Cancer Res. | volume = 61 | issue = 14 | pages = 5562–9 | year = 2001 | month = July | pmid = 11454708 | doi = | url = http://cancerres.aacrjournals.org/cgi/content/abstract/61/14/5562 | issn = ] and brain cancers (gliomas),cite journal | author = Su G, Meyer K, Nandini CD, Qiao D, Salamat S, Friedl A | title = Glypican-1 is frequently overexpressed in human gliomas and enhances FGF-2 signaling in glioma cells | journal = Am. J. Pathol. | volume = 168 | issue = 6 | pages = 2014–26 | year = 2006 | month = June | pmid = 16723715 | pmc = 1606624 | doi = 10.2353/ajpath.2006.050800 | url = | issn = ] while glypican-3 is overexpressed in liver cancers.cite journal | author = Pang RW, Joh JW, Johnson PJ, Monden M, Pawlik TM, Poon RT | title = Biology of hepatocellular carcinoma | journal = Ann. Surg. Oncol. | volume = 15 | issue = 4 | pages = 962–71 | year = 2008 | month = April | pmid = 18236113 | doi = 10.1245/s10434-007-9730-z | url = | issn = ]

tructure

All glypicans contain an N-terminal signal peptide and a hydrophobic domain in their C-terminal region, required for attachment of the GPI anchor. The amino acid sequences of the six vertebrate glypican family members vary from being 17% to 63% identical. [cite journal | author = De Cat, B, David, G. | title = Developmental roles of the glypicans | journal = Semin. Cell. Dev. Biol. | year=2001 | volume=12 | issue=2 | pages=117–125 | pmid = 11292377 | doi = 10.1006/scdb.2000.0240] The location of 14 cysteine amino acids is conserved between the glypicans, suggesting the existence of a highly similar three-dimensional structure. Heparan sulfate glycosaminoglycan chains are attached at the 50 amino acids at the C-terminal end of the protein, near the anchor and the cell membrane. [cite journal | author = Saunders S, Paine-Saunders S, and Lander AD. | title = Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain | journal = Dev. Biol. | year=1997 | volume=190 | issue=1 | pages=78–93 | pmid = 9331333 | doi = 10.1006/dbio.1997.8690]

Genes

References