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Cell surface glypicans are low-affinity endostatin receptors. Mol Cell 2001 Apr;7(4):811-22

Date

05/05/2001

Pubmed ID

11336704

DOI

10.1016/s1097-2765(01)00225-8

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.

Author List

Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B, Dhanabal M, Hanai JI, Venkataraman G, Shriver Z, Keiser N, Kalluri R, Zeng H, Mukhopadhyay D, Chen RL, Lander AD, Hagihara K, Yamaguchi Y, Sasisekharan R, Cantley L, Sukhatme VP

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

3T3 Cells
Animals
CHO Cells
Cloning, Molecular
Collagen
Collagen Type XVIII
Cricetinae
Endostatins
Endothelium
Gene Expression
Heparan Sulfate Proteoglycans
Heparin
Kidney Tubules
Membrane Proteins
Mice
Oligosaccharides
Peptide Fragments
Protein Binding
Rats
Sulfates
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