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 The heparin-binding domain of IGFBP-2 has insulin-like growth factor binding-independent biologic activity in the growing skeleton.

2011 ◽  
Vol 286 (50) ◽  
pp. 43588.2-43588
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

Plasmin degradation of insulin-like growth factor-binding protein-5 (IGFBP-5): regulation by IGFBP-5-(201—218)

1997 ◽  
Vol 273 (5) ◽  
pp. E996-E1004 ◽  
Author(s):  
Phil G. Campbell ◽  
Dennis L. Andress
Keyword(s):  
Growth Factor ◽  
Solid Phase ◽  
Binding Protein ◽  
Competitive Inhibitor ◽  
Binding Domain ◽  
Tissue Type ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Heparin Binding Domain

Using the major bone insulin-like growth factor-binding protein (IGFBP) IGFBP-5, we took a mechanistic approach in evaluating the role of the heparin-binding domain of IGFBP-5 in regulating plasmin (Pm) proteolysis of IGFBP-5. Using synthetic IGFBP-5 peptide fragments, we determined that the heparin-binding domain, IGFBP-5-(208—218), inhibits Pm proteolysis of intact IGFBP-5. The mechanism of action of IGFBP-5-(201—218) was by inhibiting Pm binding to substrate IGFBP-5. IGFBP-5-(201—218) action was independent of site of proteolysis, fluid, or solid phase interaction. In addition, IGFBP-5-(201—218) was found to inhibit plasminogen (Pg) activation to Pm. IGFBP-5-(201—218) did not directly inhibit the activity of Pm, urokinase Pg activator (PA), or tissue-type PA but acted as a competitive inhibitor of Pg activation by PA, which is in contrast to the stimulating effect of heparin on Pg activation. These data indicate that the heparin-binding domain contains the serine protease (Pg-to-Pm) binding site region of IGFBP-5, and that this region, which is presumed to represent a Pm-induced proteolytic product of IGFBP-5, is capable of regulating Pm action.

The Heparin Binding Domain of Insulin-Like Growth Factor Binding Protein (IGFBP)-3 Increases Susceptibility of IGFBP-3 to Proteolysis

1999 ◽  
Vol 31 (02/03) ◽  
pp. 216-225 ◽  
Author(s):  
Susan Durham ◽  
A. Suwanichkul ◽  
J. Hayes ◽  
A. Herington ◽  
D. Powell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Binding Domain ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Heparin Binding Domain ◽  
Igfbp 3

Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3

1998 ◽  
Vol 275 (2) ◽  
pp. E321-E331 ◽  
Author(s):  
Phil G. Campbell ◽  
Susan K. Durham ◽  
Adisak Suwanichkul ◽  
James D. Hayes ◽  
David R. Powell
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Binding Domain ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Binding Studies ◽  
Igf I ◽  
Heparin Binding Domain ◽  
Igfbp 3

Limited proteolysis lowers affinity of insulin-like growth factor (IGF)-binding protein (IGFBP)-3 for bound IGFs, resulting in greater IGF bioavailability. Plasmin is one of many proteases that cleave IGFBP-3, and the plasmin system may regulate IGFBP-3 proteolysis and IGF bioavailability in cultured cells in vitro. A role for the plasmin system in IGFBP-3 proteolysis in vivo is suggested by data presented here showing that IGFBP-3 binds plasminogen (Pg; Glu-Pg) with a dissociation constant ( Kd) ranging from 1.43 to 3.12 nM. IGF-I and Glu-Pg do not compete for IGFBP-3 binding; instead, the binary IGFBP-3/Glu-Pg complex binds IGF-I with high affinity ( Kd= 0.47 nM) to form a ternary complex. Competitive binding studies suggest that the kringle 1, 4, and 5 domains of Glu-Pg and the heparin-binding domain of IGFBP-3 participate in forming the IGFBP-3/Glu-Pg complex, and other studies show that Glu-Pg in this complex is activated at a normal rate by tissue Pg activator. Importantly, IGFBP-3/Glu-Pg complexes were detected in both human citrate plasma and serum, indicating that these complexes exist in vivo. Binding of IGFBP-3 to Glu-Pg in vivo suggests how Glu-Pg activation can specifically lead to IGFBP-3 proteolysis with subsequent release of IGFs to local target tissues.

The Heparin Binding Domain of Vitronectin Is the Region that Is Required to Enhance Insulin-Like Growth Factor-I Signaling

2006 ◽  
Vol 20 (4) ◽  
pp. 881-892 ◽  
Author(s):  
Laura A. Maile ◽  
Walker H. Busby ◽  
Kevin Sitko ◽  
Byron E. Capps ◽  
Tiffany Sergent ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Domain ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor I ◽  
Heparin Binding Domain ◽  
Growth Factor I

Insulin-like growth factor (IGF)-binding protein-5-(201—218) region regulates hydroxyapatite and IGF-I binding

1997 ◽  
Vol 273 (5) ◽  
pp. E1005-E1013 ◽  
Author(s):  
Phil G. Campbell ◽  
Dennis L. Andress
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Fluid Phase ◽  
Binding Domain ◽  
Free Fluid ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Igf I ◽  
Heparin Binding Domain ◽  
Igf Binding

Insulin-like growth factor-binding protein-5 (IGFBP-5), the major bone IGFBP, modifies the biological activity of IGFs within the osteoblastic pericellular environment. Because glycosaminoglycans modulate IGFBP-5 binding to osteoblast organic extracellular matrix (ECM), we assessed whether the heparin binding domain of IGFBP-5, IGFBP-5-(102—218), modifies the interaction of IGFBP-5 with the inorganic bone ECM hydroxyapatite (HA). Synthetic IGFBP-5-(201—218) peptide increased the binding of IGFBP-5 to HA as well as the binding of IGF-I to HA-bound IGFBP-5. This action was specific for the heparin-binding domain, because IGFBP-5-(130—138), IGFBP-5-(138—152), and IGFBP-5-(1—169) were without effect. IGFBP-5-(201—218) was found to bind directly to IGFBP-5 and cause a threefold enhancement of the IGF-I binding affinity for IGFBP-5, whether IGFBP-5 was bound to HA or was in a matrix-free fluid phase. Heparin inhibited the binding of IGFBP-5 to HA and blocked the interaction of IGFBP-5 with IGFBP-5-(201—218) in the fluid phase, suggesting that the primary heparin-binding domain of IGFBP-5 specifically enhances the binding of IGFBP-5 to HA and increases IGF-I binding to IGFBP-5.

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

Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration

1997 ◽  
Vol 273 (6) ◽  
pp. F899-F906 ◽  
Author(s):  
Christine K. Abrass ◽  
Anne K. Berfield ◽  
Dennis L. Andress
Keyword(s):  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Binding Protein ◽  
Interactive Effects ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Induction Mechanism ◽  
Igf I ◽  
Heparin Binding Domain

Insulin-like growth factor I (IGF-I) binding protein-5 (IGFBP-5) is produced by mesangial cells (MCs) and likely functions to modulate glomerular IGF-I activity. Although IGFBP-5 may be inhibitory for IGF-stimulated MC activity, preliminary studies suggested that IGFBP-5 acts directly on MCs. To investigate this further, we evaluated the effects of IGFBP-5 on rat MC migration. We found that the carboxy-truncated fragment, IGFBP-5-(1–169), inhibited IGF-I-stimulated migration, but intact IGFBP-5 simulated migration when IGF-I was not present. Demonstration that125I-labeled IGFBP-5 directly binds to MCs further supports an independent role for IGFBP-5. Because heparin inhibited MC binding of125I-IGFBP-5, we tested the heparin binding peptide, IGFBP-5-(201–218), for stimulatory activity. IGFBP-5-(201–218) stimulated MC migration, and this effect was inhibited by heparin. Because the disintegrin, kistrin, blocked IGF-I-induced migration but not migration induced by IGFBP-5-(201–218), the migratory induction mechanism for the two peptides is different. These data indicate that separate, specific regions of IGFBP-5 are responsible for interactive effects with IGF-I as well as direct effects on MC activity.

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