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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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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

Genetic evidence that FGFs have an instructive role in limb proximal–distal patterning

TL;DR: Analysis of the compound mutant limb buds revealed that, in addition to sustaining cell survival, AER-FGFs regulate P–D-patterning gene expression during early limb bud development, providing genetic evidence that A ER-F GFs function to specify a distal domain and challenging the long-standing hypothesis that AER -FGF signalling is permissive rather than instructive for limb patterning.
Journal ArticleDOI

PPARα is a key regulator of hepatic FGF21

TL;DR: It is shown that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARalpha), and the potential importance of PPARalpha for FGF 21 expression also in human liver was shown by Wy-14,643 induction of F GF21 mRNA in human primary hepatocytes.
Journal ArticleDOI

βKlotho Is Required for Fibroblast Growth Factor 21 Effects On Growth and Metabolism

TL;DR: It is demonstrated that βKlotho is essential for FGF21 activity and thatβKlothso in adipose tissue contributes to the beneficial metabolic actions of FGF 21.
Journal ArticleDOI

Compensation by Fibroblast Growth Factor 1 (FGF1) Does Not Account for the Mild Phenotypic Defects Observed in FGF2 Null Mice

TL;DR: The results suggest that the relatively mild defects in FGF2 knockout animals are not a consequence of compensation by FGF1 and suggest highly restricted roles for both factors under normal developmental and physiological conditions.
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