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Abstract
Human fibroblast growth factor 1 (FGF-1) is one of the best characterized members of the FGF superfamily. FGF-1 is a powerful mitogen exhibiting strong action on numerous different cell types. It plays a role in various stages of development and morphogenesis, as well as in angiogenesis and wound healing processes. Engineering of FGFs can bring many advantages. Design and construction of different mutants can contribute to a better understanding of the mechanism of action of protein growth factors. Moreover, application of FGFs as recombinant polypeptides in the treatment of wound and fracture healing, cardiovascular diseases and neurodegenerative diseases seems to be a rational medical approach. However, low thermal stability and high sensitivity to proteases limit the potential pharmaceutical use of wild-type FGFs. Thus, advanced protein design techniques and recombinant protein production can help to obtain new variants of FGFs with radically increased thermodynamic stability, prolonged half-life and improved proteolytic resistance. Such studies can provide a good starting point to convert short-lived and/or sensitive growth factors to effective therapeutic proteins.
| Abbreviations | ||
| CAD, | = | coronary artery disease; |
| CD, | = | circular dichroism; |
| CLI, | = | critical limb ischemia; |
| DAG, | = | diacylglycerol; |
| ECM, | = | extracellular matrix; |
| EGF, | = | epidermal growth factor; |
| EGFR, | = | epidermal growth factor receptor; |
| ER, | = | endoplasmic reticulum; |
| FAK, | = | focal adhesion kinase; |
| FHF, | = | fibroblast growth factor homologous factor; |
| FIF, | = | FGF-2-interacting-factor; |
| FGF, | = | fibroblast growth factor; |
| FGFR, | = | fibroblast growth factor receptor; |
| Gab1, | = | Grb2-associated binder 1; |
| GdmCl, | = | guanidinium chloride; |
| Grb2, | = | growth factor receptor-bound protein 2; |
| HSPGs, | = | heparan sulfate proteoglycans; |
| IC, | = | intermittent claudication; |
| IL, | = | interleukin; |
| IP3, | = | inositol triphosphate; |
| MAPK, | = | mitogen-activated protein kinase; |
| MG, | = | molten globule; |
| MMP, | = | matrix metalloproteinase; |
| NLS, | = | nuclear location signal; |
| NIH, | = | National Institute of Health; |
| PAD, | = | peripheral artery disease; |
| PDB, | = | Protein Data Bank; |
| PDGF, | = | platelet-derived growth factor; |
| PDK, | = | phosphoinositide-dependent kinase; |
| PI3K, | = | phosphoinositide 3-kinase; |
| PKC, | = | protein kinase C; |
| PLCγ, | = | phospholipase Cγ; |
| Sos, | = | Son of sevenless; |
| TGF, | = | transforming growth factor; |
| TALISMAN, | = | Therapeutic Angiogenesis With Intramuscular NV1FGF in Patients With Critical Limb Ischemia; |
| TLS, | = | translation/libration/screw; |
| TRAFFIC, | = | Therapeutic Angiogenesis with recombinant Fibroblast growth Factor for Intermittent Claudication; |
| UPA, | = | urokinase-type plasminogen activator; |
| VEGF, | = | vascular endothelial growth factor |
| Abbreviations | ||
| CAD, | = | coronary artery disease; |
| CD, | = | circular dichroism; |
| CLI, | = | critical limb ischemia; |
| DAG, | = | diacylglycerol; |
| ECM, | = | extracellular matrix; |
| EGF, | = | epidermal growth factor; |
| EGFR, | = | epidermal growth factor receptor; |
| ER, | = | endoplasmic reticulum; |
| FAK, | = | focal adhesion kinase; |
| FHF, | = | fibroblast growth factor homologous factor; |
| FIF, | = | FGF-2-interacting-factor; |
| FGF, | = | fibroblast growth factor; |
| FGFR, | = | fibroblast growth factor receptor; |
| Gab1, | = | Grb2-associated binder 1; |
| GdmCl, | = | guanidinium chloride; |
| Grb2, | = | growth factor receptor-bound protein 2; |
| HSPGs, | = | heparan sulfate proteoglycans; |
| IC, | = | intermittent claudication; |
| IL, | = | interleukin; |
| IP3, | = | inositol triphosphate; |
| MAPK, | = | mitogen-activated protein kinase; |
| MG, | = | molten globule; |
| MMP, | = | matrix metalloproteinase; |
| NLS, | = | nuclear location signal; |
| NIH, | = | National Institute of Health; |
| PAD, | = | peripheral artery disease; |
| PDB, | = | Protein Data Bank; |
| PDGF, | = | platelet-derived growth factor; |
| PDK, | = | phosphoinositide-dependent kinase; |
| PI3K, | = | phosphoinositide 3-kinase; |
| PKC, | = | protein kinase C; |
| PLCγ, | = | phospholipase Cγ; |
| Sos, | = | Son of sevenless; |
| TGF, | = | transforming growth factor; |
| TALISMAN, | = | Therapeutic Angiogenesis With Intramuscular NV1FGF in Patients With Critical Limb Ischemia; |
| TLS, | = | translation/libration/screw; |
| TRAFFIC, | = | Therapeutic Angiogenesis with recombinant Fibroblast growth Factor for Intermittent Claudication; |
| UPA, | = | urokinase-type plasminogen activator; |
| VEGF, | = | vascular endothelial growth factor |
Notes
*Editor's note: A docking protein that mediates intracellular signals.
†Editor's note: A calcium-binding motif composed of two helixes (E and F) joined by a loop.