scholarly journals Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery

10.3791/54202 ◽  
2016 ◽  
Author(s):  
Raymond Wing Moon Lam ◽  
Sunny Akogwu Abbah ◽  
Wang Ming ◽  
Mathanapriya Naidu ◽  
Felly Ng ◽  
...  
Keyword(s):  
Growth Factor ◽  
Polyelectrolyte Complex ◽  
Binding Domain ◽  
Growth Factor Delivery ◽  
Heparin Binding ◽  
Heparin Binding Domain

scholarly journals The Heparin-binding Domain of IGFBP-2 Has Insulin-like Growth Factor Binding-independent Biologic Activity in the Growing Skeleton

2011 ◽  
Vol 286 (16) ◽  
pp. 14670-14680 ◽  
Author(s):  
Masanobu Kawai ◽  
Anne C. Breggia ◽  
Victoria E. DeMambro ◽  
Xinchun Shen ◽  
Ernesto Canalis ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Domain ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Biologic Activity ◽  
Heparin Binding Domain

scholarly journals Solution structure of the heparin-binding domain of vascular endothelial growth factor

Structure ◽  
1998 ◽  
Vol 6 (5) ◽  
pp. 637-648 ◽  
Author(s):  
Wayne J Fairbrother ◽  
Mark A Champe ◽  
Hans W Christinger ◽  
Bruce A Keyt ◽  
Melissa A Starovasnik
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Solution Structure ◽  
Binding Domain ◽  
Vascular Endothelial ◽  
Heparin Binding ◽  
Heparin Binding Domain ◽  
Endothelial Growth Factor

scholarly journals Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lumeng J. Yu ◽  
Victoria H. Ko ◽  
Duy T. Dao ◽  
Jordan D. Secor ◽  
Amy Pan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Functional Outcomes ◽  
Growth Factor Receptor ◽  
Binding Domain ◽  
Heparin Binding ◽  
Lung Growth ◽  
Compensatory Lung Growth ◽  
Heparin Binding Domain ◽  
Left Pneumonectomy

AbstractMorbidity and mortality for neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia remains high. These patients may be deficient in vascular endothelial growth factor (VEGF). Our lab previously established that exogenous VEGF164 accelerates compensatory lung growth (CLG) after left pneumonectomy in a murine model. We aimed to further investigate VEGF-mediated CLG by examining the role of the heparin-binding domain (HBD). Eight-week-old, male, C57BL/6J mice underwent left pneumonectomy, followed by post-operative and daily intraperitoneal injections of equimolar VEGF164 or VEGF120, which lacks the HBD. Isovolumetric saline was used as a control. VEGF164 significantly increased lung volume, total lung capacity, and alveolarization, while VEGF120 did not. Treadmill exercise tolerance testing (TETT) demonstrated improved functional outcomes post-pneumonectomy with VEGF164 treatment. In lung protein analysis, VEGF treatment modulated downstream angiogenic signaling. Activation of epithelial growth factor receptor and pulmonary cell proliferation was also upregulated. Human microvascular lung endothelial cells (HMVEC-L) treated with VEGF demonstrated decreased potency of VEGFR2 activation with VEGF121 treatment compared to VEGF165 treatment. Taken together, these data indicate that the VEGF HBD contributes to angiogenic and proliferative signaling, is required for accelerated compensatory lung growth, and improves functional outcomes in a murine CLG model.

The heparin-binding domain of amphiregulin necessitates the precursor pro-region for growth factor secretion

1994 ◽  
Vol 14 (3) ◽  
pp. 1635-1646
Author(s):  
B A Thorne ◽  
G D Plowman
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Binding Domain ◽  
Biologically Active ◽  
Structural Motif ◽  
Heparin Binding ◽  
Active Growth ◽  
Heparin Binding Domain ◽  
Pro Region

The five members of the human epidermal growth factor (EGF) family (EGF, transforming growth factor alpha [TGF-alpha], heparin-binding EGF-like growth factor [HB-EGF], betacellulin, and amphiregulin [AR]) are synthesized as transmembrane proteins whose extracellular domains are proteolytically processed to release the biologically active mature growth factors. These factors all activate the EGF receptor, but in contrast to EGF and TGF-alpha, the mature forms of HB-EGF and AR are also glycosylated, heparin-binding proteins. We have constructed a series of mutants to examine the influence of the distinct precursor domains in the biosynthesis of AR. The transmembrane and cytoplasmic domains of the precursor are not required for secretion of bioactive AR from either COS or mammary epithelium-derived cells, although proteolytic removal of the N-terminal pro-region is less efficient in the absence of the membrane anchor. Deletion of the N-terminal pro-region, however, results in rapid intracellular degradation of the molecule with no detectable secretion of active growth factor. AR secretion is preserved by replacing the native pro-region with the corresponding domain of the HB-EGF precursor but not with that of the TGF-alpha precursor. In the absence of any N-terminal pro-region, secretion of the molecule is restored by deleting the N-terminal heparin-binding domain of mature AR. Both EGF and TGF-alpha, in contrast, can be secreted without their pro-regions. However, if the protein is fused with the AR heparin-binding domain, TGF-alpha secretion is inhibited unless the AR pro-region is also present. We propose that the heparin-binding domain of mature AR necessitates the presence of a specific structural motif in an N-terminal pro-region to permit proper folding, and thus secretion, of a bioactive molecule.

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