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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

FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner

TL;DR: It is demonstrated for the first time that FHF1 directly interacts with all four major FGFRs, emphasizing much greater similarity between FHFs and canonical FGFs than previously indicated.
Journal ArticleDOI

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair.

TL;DR: A comprehensive understanding of the mechanism of action for multifunctional fibroblast growth factor (FGF) signaling in the biology of the heart is a matter of high importance as discussed by the authors.
Journal ArticleDOI

Current Understanding of the Genetics of Intervertebral Disc Degeneration.

TL;DR: Preliminary data from studies investigating F GF4 retrogenes in IVDD implicate FGF4 overexpression as a major disease factor, they have highlighted knowledge gaps in the understanding of intervertebral disc herniation which is a complex and multifactorial disease process.
Journal ArticleDOI

FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance.

TL;DR: In this paper, a review brings together information on the mechanisms underlying the involvement of the FGF/FGFR axis in the generation of drug resistance in cancer and highlights the need for further research to overcome this serious problem with novel therapeutic strategies.
Journal ArticleDOI

The therapeutic targeting of the FGFR1/Src/NF-κB signaling axis inhibits pancreatic ductal adenocarcinoma stemness and oncogenicity

TL;DR: It is concluded that PD173074 suppresses the tumorigenesis and CSCs-like phenotype of PDAC cells, highlighting its therapeutic efficacy and providing support for its potential use as a therapeutic option for the ‘difficult- to-treat’, ‘quick-to-relapse’ PDAC patients.
References
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Journal ArticleDOI

AKT/PKB signaling: navigating downstream.

TL;DR: Those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration are discussed.
Journal ArticleDOI

The Wnt signaling pathway in development and disease.

TL;DR: The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs.
Journal ArticleDOI

Mutation of the mouse klotho gene leads to a syndrome resembling ageing

TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, and may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.

Mutation of the mouse klotho gene leads to a syndrome resembling ageing

TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, including short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema as mentioned in this paper.
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.
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