Fibroblast growth factors, their receptors and signaling.
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.read more
Citations
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Evidence that heparin saccharides promote FGF2 mitogenesis through two distinct mechanisms.
Sarah J. Goodger,Christopher J. Robinson,Kevin J. Murphy,Nijole Gasiunas,Nicholas J. Harmer,Nicholas J. Harmer,Tom L. Blundell,David A. Pye,John T. Gallagher +8 more
TL;DR: Heparin-like saccharides play an essential role in binding to both fibroblast growth factors (FGF) and their receptors at the cell surface and their ability to support FGF2 mitogenesis of heparan sulfate-deficient cells expressing FGFR1c is investigated.
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Fibroblast growth factor-2 maintains the differentiation potential of nucleus pulposus cells in vitro: implications for cell-based transplantation therapy.
Tsung-Ting Tsai,Asha Guttapalli,Erbil Oguz,Lih-Huei Chen,Alexander R. Vaccaro,Todd J. Albert,Irving M. Shapiro,Makarand V. Risbud +7 more
TL;DR: The presence of FGF-2 during culture expansion of nucleus pulposus cells in monolayer can sustain a differentiated cell phenotype by maintaining responsiveness to TGF-&bgr;1.
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Thrombin- and Factor Xa–Induced DNA Synthesis Is Mediated by Transactivation of Fibroblast Growth Factor Receptor-1 in Human Vascular Smooth Muscle Cells
TL;DR: The data suggest that in human vascular SMCs, both thrombin and FXa rapidly release bFGF into the pericellular matrix, which is followed by transactivation of the FGFR-1 and increased proliferation.
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Nuclear and Nucleolar Localization of 18-kDa Fibroblast Growth Factor-2 Is Controlled by C-terminal Signals
TL;DR: Together, these results demonstrate that the 18-kDa FGF-2 harbors a C-terminal nonclassical bipartite NLS, a portion of which also regulates its nucleolar localization.
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Heparan Sulfate-related Oligosaccharides in Ternary Complex Formation with Fibroblast Growth Factors 1 and 2 and Their Receptors
Nadja Jastrebova,Maarten Vanwildemeersch,Alan C. Rapraeger,Guillermo Giménez-Gallego,Ulf Lindahl,Dorothe Spillmann +5 more
TL;DR: In all systems studied, the stability of FGF-oligosaccharide-FR complexes correlated with the overall level of saccharide O-sulfation rather than on the precise distribution of sulfate groups.
References
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Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
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Thalidomide is an inhibitor of angiogenesis.
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Receptor specificity of the fibroblast growth factor family.
David M. Ornitz,Jingsong Xu,Jennifer S. Colvin,Donald G. McEwen,Craig A. MacArthur,François Coulier,Guangxia Gao,Mitchell Goldfarb +7 more
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.