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Open AccessJournal ArticleDOI

The Fibroblast Growth Factor signaling pathway

TLDR
Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning.
Abstract
The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs) Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer © 2015 Wiley Periodicals, Inc

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Citations
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Journal ArticleDOI

Tumor angiogenesis: causes, consequences, challenges and opportunities.

TL;DR: The current understanding of cellular and molecular mechanisms involved in tumor angiogenesis is summarized and challenges and opportunities associated with vascular targeting are discussed.
Journal ArticleDOI

Fibroblast growth factor signaling in skeletal development and disease

TL;DR: Progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis is examined, and the mechanisms by which mutations in FGF signalling molecules cause skeletal malformations in humans are explored.
Journal ArticleDOI

The molecular basis of endothelial cell plasticity

TL;DR: The endothelium is capable of remarkable plasticity in the embryo and in the adult, maintenance of differentiated endothelial state is an active process requiring constant signalling input that leads to the development of endothelial-to-mesenchymal transition that plays an important role in pathogenesis of a number of diseases.
References
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Journal ArticleDOI

FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains.

TL;DR: It is shown that lung mesenchyme can be divided into two distinct regions: the sub-mesothelial and sub-epithelial compartments, which proliferate in response to unique growth factor signals, and the pattern and expression levels of mesenchymal growth factors that signal back to the epithelium.
Journal ArticleDOI

A Lys644Glu Substitution in Fibroblast Growth Factor Receptor 3 (FGFR3) Causes Dwarfism in Mice by Activation of STATs and Ink4 Cell Cycle Inhibitors

TL;DR: Molecular analysis revealed that expression of the mutant receptor caused the activation of Stat1, Stat5a and Stat5b, and the up-regulation of p16, p18 and p19 cell cycle inhibitors, leading to dramatic expansion of the resting zone of chondrocytes at the expense of the proliferating chondROcytes.
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FGF19-induced Hepatocyte Proliferation Is Mediated through FGFR4 Activation

TL;DR: It is determined that amino acids residues 38–42 of FGF19 are sufficient to confer bothFGFR4 activation and increased hepatocyte proliferation in vivo to FGF21, suggesting that activation of FGFR4 is the mechanism whereby FGF 19 can increase hepatocytes proliferation and induce hepatocellular carcinoma formation.
Journal ArticleDOI

Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome

TL;DR: The crystal structures of these two FGFR2 mutants in complex with fibroblast growth factor 2 (FGF2) demonstrate that both mutations introduce additional interactions betweenFGFR2 and FGF2, thereby augmenting FGFR1–FGF1 affinity and it is proposed that the Pro-253 → Arg mutation will indiscriminately increase the affinity of FG FR2 toward any FGF.
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