Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions.
Heparanase, an endo-beta-D-glucuronidase, is involved in numerous normal physiological and pathological processes, such as inflammation, wound healing and tumour metastasis/angiogenesis, through its ability to mediate the degradation of heparan sulfate, a key structural component of the extracellular matrix and on the surface of cells. Identifying endogenous molecules that can regulate heparanase activity will aid the understanding of its molecular function in health and disease and provide the potential for development of novel anti-cancer and anti-inflammatory therapeutics. The ability of the extracellular heparanase to tether onto cell surface heparan sulfate proteoglycans and other receptor(s), such as the cation-independent mannose-6-phosphate receptor, is key to its activation, function and uptake into intracellular compartments. Here we describe experiments demonstrating that a relatively abundant plasma glycoprotein, histidine-rich glycoprotein, directly interacts with platelet-derived heparanase and enhances its enzymatic activity. The findings in this study also show that histidine-rich glycoprotein interferes with heparanase binding to cell surface receptors, particularly heparan sulfate proteoglycans. Thus, the interaction between histidine-rich glycoprotein and heparanase can potentially regulate the role of heparanase in a variety of physiological and pathological conditions.
Poon
Ivan K H
IK
Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra 2601, Australia.
Yee
Dean Y
DY
Jones
Allison L
AL
Wood
Robert J
RJ
Davis
David S
DS
Freeman
Craig
C
Parish
Christopher R
CR
Hulett
Mark D
MD
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D005966:Glucuronidase / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D000099053:Histidine-Rich Glycoprotein; D000099175:Heparanase
D005966:Glucuronidase; D006023:Glycoproteins; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D000099175:Heparanase