Isolation and Conformational Analysis of Fragment Peptide Corresponding to the Heparin-Binding Site of Hepatocyte Growth Factor

Biochemistry ◽  
1997 ◽  
Vol 36 (33) ◽  
pp. 10286-10291 ◽  
Author(s):  
Hideyuki Aoyama ◽  
Daiji Naka ◽  
Yoshiko Yoshiyama ◽  
Takehisa Ishii ◽  
Jun Kondo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Conformational Analysis ◽  
Binding Site ◽  
Heparin Binding ◽  
Heparin Binding Site ◽  
Hepatocyte Growth

scholarly journals The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site

Structure ◽  
1998 ◽  
Vol 6 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Hongjun Zhou ◽  
Marie J Mazzulla ◽  
Joshua D Kaufman ◽  
Stephen J Stahl ◽  
Paul T Wingfield ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Binding Site ◽  
Solution Structure ◽  
Heparin Binding ◽  
Terminal Domain ◽  
Heparin Binding Site ◽  
Hepatocyte Growth

scholarly journals Identification and Dynamics of a Heparin-Binding Site in Hepatocyte Growth Factor†

Biochemistry ◽  
1999 ◽  
Vol 38 (45) ◽  
pp. 14793-14802 ◽  
Author(s):  
Hongjun Zhou ◽  
José R. Casas-Finet ◽  
R. Heath Coats ◽  
Joshua D. Kaufman ◽  
Stephen J. Stahl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Binding Site ◽  
Heparin Binding ◽  
Heparin Binding Site ◽  
Hepatocyte Growth

High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3139-3146 ◽  
Author(s):  
Carina Seidel ◽  
Magne Børset ◽  
Øyvind Hjertner ◽  
Dianjun Cao ◽  
Niels Abildgaard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Heparan Sulfate ◽  
Cell Line ◽  
Osteosarcoma Cell ◽  
Heparin Binding ◽  
Myeloma Cells ◽  
Hepatocyte Growth

Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells with purified soluble syndecan-1 could effectively displace HGF from the cell surface, suggesting that soluble syndecan-1 can act as a carrier for HGF in vivo. Finally, using a sensitive HGF bioassay (interleukin-11 production from the osteosarcoma cell line Saos-2) and intact syndecan-1 isolated from the U-266 myeloma cell line, we found that the presence of high concentrations of syndecan-1 (more than 3 μg/mL) inhibited the HGF effect, whereas lower concentrations potentiated it. HGF is only one of several heparin-binding cytokines associated with myeloma. These data indicate that soluble syndecan-1 may participate in the pathology of myeloma by modulating cytokine activity within the bone marrow.

Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2997-3004 ◽  
Author(s):  
Alain Grenier ◽  
Sylvie Chollet-Martin ◽  
Bruno Crestani ◽  
Charlotte Delarche ◽  
Jamel El Benna ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Messenger Rna ◽  
Polymorphonuclear Neutrophils ◽  
Heparin Binding ◽  
Single Chain ◽  
Diisopropyl Fluorophosphate ◽  
Binding Factor ◽  
Hepatocyte Growth ◽  
Major Mediator

Abstract Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration.

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