Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling
Open Access
- 21 February 2011
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 192 (4), 691-704
- https://doi.org/10.1083/jcb.201008087
Abstract
Glypican-5 (GPC5) is one of the six members of the glypican family. It has been previously reported that GPC5 stimulates the proliferation of rhabdomyosarcoma cells. In this study, we show that this stimulatory activity of GPC5 is a result of its ability to promote Hedgehog (Hh) signaling. We have previously shown that GPC3, another member of the glypican family, inhibits Hh signaling by competing with Patched 1 (Ptc1) for Hh binding. Furthermore, we showed that GPC3 binds to Hh through its core protein but not to Ptc1. In this paper, we demonstrate that GPC5 increases the binding of Sonic Hh to Ptc1. We also show that GPC5 binds to both Hh and Ptc1 through its glycosaminoglycan chains and that, unlike GPC3, GPC5 localizes to the primary cilia. Interestingly, we found that the heparan sulfate chains of GPC5 display a significantly higher degree of sulfation than those of GPC3. Based on these results, we propose that GPC5 stimulates Hh signaling by facilitating/stabilizing the interaction between Hh and Ptc1.Keywords
This publication has 53 references indexed in Scilit:
- Dally-like core protein and its mammalian homologues mediate stimulatory and inhibitory effects on Hedgehog signal responseProceedings of the National Academy of Sciences of the United States of America, 2010
- Lateral transport of Smoothened from the plasma membrane to the membrane of the ciliumThe Journal of cell biology, 2009
- Inhibition of the Hedgehog Pathway in Advanced Basal-Cell CarcinomaNew England Journal of Medicine, 2009
- Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449New England Journal of Medicine, 2009
- Investigating the Elusive Mechanism of Glycosaminoglycan BiosynthesisPublished by Elsevier BV ,2009
- Overgrowth of a mouse model of Simpson– Golabi–Behmel syndrome is partly mediated by Indian HedgehogEMBO Reports, 2009
- Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machineryThe Journal of cell biology, 2008
- Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surfaceDevelopmental Biology, 2008
- The Gli code: an information nexus regulating cell fate, stemness and cancerTrends in Cell Biology, 2007
- Heparan sulphate proteoglycans fine-tune mammalian physiologyNature, 2007