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.[1]
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.[2] Extracellular localization of the other glypican in Drosophila, dally-like, is also required for the proper level of Hedgehog signaling in the developing wing.[3]
In humans, glypican-1 is overexpressed in breast[4] and brain cancers (gliomas),[5] while glypican-3 is overexpressed in liver cancers.[6]
Structure
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.[7] 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.[8]
References
- ^ Filmus, J. (2001). "Glypicans in growth control and cancer". Glycobiology 11 (3): 19R–23R. doi:10.1093/glycob/11.3.19R. PMID 11320054.
- ^ Crickmore MA, Mann RS (January 2007). "Hox control of morphogen mobility and organ development through regulation of glypican expression". Development 134 (2): 327–34. doi:10.1242/dev.02737. PMID 17166918.
- ^ Gallet A, Staccini-Lavenant L, Thérond PP (May 2008). "Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis". Dev. Cell 14 (5): 712–25. doi:10.1016/j.devcel.2008.03.001. PMID 18477454.
- ^ Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M (July 2001). "Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells". Cancer Res. 61 (14): 5562–9. PMID 11454708. http://cancerres.aacrjournals.org/cgi/content/abstract/61/14/5562.
- ^ Su G, Meyer K, Nandini CD, Qiao D, Salamat S, Friedl A (June 2006). "Glypican-1 is frequently overexpressed in human gliomas and enhances FGF-2 signaling in glioma cells". Am. J. Pathol. 168 (6): 2014–26. doi:10.2353/ajpath.2006.050800. PMC 1606624. PMID 16723715. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1606624.
- ^ Pang RW, Joh JW, Johnson PJ, Monden M, Pawlik TM, Poon RT (April 2008). "Biology of hepatocellular carcinoma". Ann. Surg. Oncol. 15 (4): 962–71. doi:10.1245/s10434-007-9730-z. PMID 18236113.
- ^ De Cat, B, David, G. (2001). "Developmental roles of the glypicans". Semin. Cell. Dev. Biol. 12 (2): 117–125. doi:10.1006/scdb.2000.0240. PMID 11292377.
- ^ Saunders S, Paine-Saunders S, and Lander AD. (1997). "Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain". Dev. Biol. 190 (1): 78–93. doi:10.1006/dbio.1997.8690. PMID 9331333.
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| Mucoproteins |
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| Proteoglycans |
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| Other |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i
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