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Open AccessJournal ArticleDOI

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers, +2 more
- 01 Sep 2000 - 
- Vol. 7, Iss: 3, pp 165-197
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TLDR
FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.
Abstract
Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Book ChapterDOI

Mechanisms of Brain Tumor Angiogenesis

TL;DR: This chapter summarizes data from glioma angiogenesis studies, as malignant gliomas count for nearly 40% incidence of brain tumors in humans, and results of these studies should apply to angiogenic occurring in other types of brain tumor tumors.
Journal ArticleDOI

Metabolic activation of drugs by cytochrome P450 enzymes: Biochemical insights into mechanism-based inactivation by fibroblast growth factor receptor inhibitors and chemical approaches to attenuate reactive metabolite formation.

TL;DR: In this paper , the authors summarized the fundamental aspects and consequences of P450 metabolic activation with a focus on mechanism-based inactivation (MBI) and highlighted a promising new paradigm which involves the rational deuteration of a drug molecule at its known bioactivation 'hot-spot' to shunt metabolism away from these aberrant pathways and reduce reactive metabolite formation.
DissertationDOI

Functional dissection of the "Drosophila melanogaster" fibroblast growth factor signalling pathway in branching morphogenesis of the developing tracheal system

TL;DR: The results suggest that Dof is able to interact with human FGFRs and acts specifically in the FGF signalling pathway, and the activation of Ras is not sufficient to activate the migration machinery in tracheal and mesodermal cells.
References
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Journal ArticleDOI

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
Journal ArticleDOI

Protein modules and signalling networks

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
Journal ArticleDOI

Thalidomide is an inhibitor of angiogenesis.

TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.
Journal ArticleDOI

Receptor specificity of the fibroblast growth factor family.

TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.
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