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Studies on the identification and characterization of the receptor for heparin binding growth factor 1

Thesis/Dissertation ·
OSTI ID:6325580
Receptor-binding studies using biologically active {sup 125}I-HBGF-1 revealed that many cells of mesenchymal origin possess HBGF-1 receptors with affinities ranging from 100-200 pM and 2.0 x 10{sup 3} sites per cell. The HBGF-1 receptor was identified by convalently cross-linking {sup 125}I-HBGF-1 to receptor-bearing cells with the homobifunctional reagent disuccinimidyl suberate (DSS). Cross-linking of {sup 125}I-HBGF-L to M{sub r} 150,000 and M{sub r} 130,000 cell surface polypeptides was inhibited by excess unlabeled HBGF-1 but not by other growth factors. The {sup 125}I-HBGF receptor cross-linked complex was susceptible to cleavage by cyanogen bromide and trypsin, confirming the polypeptide nature of HBGF-1 receptor. Binding studies carried at 37{degree}C and 4{degree}C demonstrated that the HBGF-1 receptor is down-regulated at 37{degree}C with internalization of {sup 125}I-HBGF-1. The degradation of internalized {sup 125}I-HBGF-1 was inhibited by the lysosomotropic agent chloroquine, suggesting that internalized {sup 125}I-HBGF-1 is directed to the lysosomal cellular compartment. The lymphokine IFN-{sub {gamma}} was shown to inhibit HBGF-1 induced proliferation of endothelial cells in a dose-dependent and reversible manner. Studies were also undertaken to determine if cells that possess HBGF-1 receptors also express the growth factor.
Research Organization:
George Washington Univ., Washington, DC (USA)
OSTI ID:
6325580
Country of Publication:
United States
Language:
English