Cell surface glypicans are low-affinity endostatin receptors

S. Ananth Karumanchi, Vivekanand Jha, Ramani Ramchandran, Anil Karihaloo, Leonidas Tsiokas, Barden Chan, Mohanraj Dhanabal, Jun Ichi Hanai, Ganesh Venkataraman, Zachary Shriver, Nishla Keiser, Raghu Kalluri, Huiyan Zeng, Debabrata Mukhopadhyay, Robert L. Chen, Arthur D. Lander, Kazuki Hagihara, Yu Yamaguchi, Ram Sasisekharan, Lloyd CantleyVikas P. Sukhatme

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

Endostatin, a collagen XVIII fragment, is a potent anti-angiogenic protein. We sought to identify its endothelial cell surface receptor(s). Alkaline phosphatase-tagged endostatin bound endothelial cells revealing two binding affinities. Expression cloning identified glypican, a cell surface proteoglycan as the lower-affinity receptor. Biochemical and genetic studies indicated that glypicans' heparan sulfate glycosaminoglycans were critical for endostatin binding. Furthermore, endostatin selected a specific octasulfated hexasaccharide from a sequence in heparin. We have also demonstrated a role for endostatin in renal tubular cell branching morphogenesis and show that glypicans serve as low-affinity receptors for endostatin in these cells, as in endothelial cells. Finally, antisense experiments suggest the critical importance of glypicans in mediating endostatin activities.

Original languageEnglish (US)
Pages (from-to)811-822
Number of pages12
JournalMolecular Cell
Volume7
Issue number4
DOIs
StatePublished - Apr 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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