Fibroblast growth factor-2 (FGF-2) is a member of the FGF family that, like FGF-1 and FGF-9, lacks a signal sequence. These proteins therefore are not secreted through the endoplasmic reticulum and Golgi apparatus. Yet these factors act outside the cell by binding to cell surface GF receptors that mediate diverse biological effects including angiogenesis, tumor growth, bone formation, mitogenesis, migration, wound healing, and neuronal survival. Currently the mechanisms leading to the cellular release of these signal sequence-deficient FGFs are not well understood very little is known about the interaction of released FGF-2 with other proteins in vivo. We have previously demonstrated that released FGF-2 is a key player in mediating responses of the vessel wall to stress and injury which are involved in vascular repair and vascular disease. We have used heparin Sepharose chromatography to purify heparin-binding proteins from plasma and serum. High molecular weight bands (>50 kDa) resistant to denaturing and reducing conditions were detected with 3 different monoclonal antibodies against FGF-2 immuno reactive bands contained plasminogen and fibrinogen. MALDI-TOF mass spectrometry revealed that the FGF-2 immuno reactive bands contained plasminogen and fibrinogen. In a 3T3 cell assay, mitogenic activity susceptible to neutralizing anti-FGF-2 antibodies was associated with the heparin Sepharose purified plasma and serum fractions. Using bovine aortic endothelial (BAE) cells we demonstrate cross-linking of endogenous FGF-2 to added plasminogen. The cross-linking of released FGF-2 to plasma proteins such as plasminogen fragments (angiostatin) could be an important event in regulating the availability of FGF-2 by affecting its half life and localization and thereby controlling processes such as angiogenesis , wound healing and tumor growth. The goals of the present application therefore are to carry out the biochemical characterization of the enzyme that cross-links FGF-2 and explore the mechanism that lead to cellular FGF-2 release. In vivo models in transgenic and gene targeted mice will be used to demonstrate the physiologic significance of these mechanisms.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Maine Medical Center
United States
Zip Code
Soley, Luna; Falank, Carolyne; Reagan, Michaela R (2017) MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells. Curr Osteoporos Rep 15:162-170
Young, K; Krebs, L T; Tweedie, E et al. (2016) Endoglin is required in Pax3-derived cells for embryonic blood vessel formation. Dev Biol 409:95-105
Ames, Jacquelyn J; Contois, Liangru; Caron, Jennifer M et al. (2016) Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. J Biol Chem 291:2731-50
Contois, Liangru W; Akalu, Abebe; Caron, Jennifer M et al. (2015) Inhibition of tumor-associated ?v?3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo. Angiogenesis 18:31-46
Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E et al. (2013) Altered thermogenesis and impaired bone remodeling in Misty mice. J Bone Miner Res 28:1885-97
Apra, Caroline; Richard, Laurence; Coulpier, Fanny et al. (2012) Cthrc1 is a negative regulator of myelination in Schwann cells. Glia 60:393-403
Contois, Liangru W; Nugent, Desiree P; Caron, Jennifer M et al. (2012) Insulin-like growth factor binding protein-4 differentially inhibits growth factor-induced angiogenesis. J Biol Chem 287:1779-89
Urs, Sumithra; Henderson, Terry; Le, Phuong et al. (2012) Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction. Br J Nutr 108:1025-33
Sathyanarayana, Pradeep; Dev, Arvind; Pradeep, Anamika et al. (2012) Spry1 as a novel regulator of erythropoiesis, EPO/EPOR target, and suppressor of JAK2. Blood 119:5522-31
Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E et al. (2012) Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain. Bone 50:490-8

Showing the most recent 10 out of 101 publications