The Fibroblast Growth Factor signaling pathway
David M. Ornitz,Nobuyuki Itoh +1 more
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, Incread more
Citations
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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
Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial.
Arun J. Sanyal,Edgar D. Charles,Brent A. Neuschwander-Tetri,Rohit Loomba,Stephen A. Harrison,Manal F. Abdelmalek,Eric Lawitz,Dina Halegoua-DeMarzio,Sudeep Kundu,Stephanie Noviello,Yi Luo,Rose C. Christian +11 more
TL;DR: Treatment with subcutaneously administered pegbelfermin for 16 weeks was generally well tolerated and significantly reduced hepatic fat fraction in patients with non-alcoholic steatohepatitis, and the full planned sample size was not needed.
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.
Journal ArticleDOI
Classifying the evolutionary and ecological features of neoplasms
Carlo C. Maley,Athena Aktipis,Trevor A. Graham,Andrea Sottoriva,Amy M. Boddy,Michalina Janiszewska,Ariosto S. Silva,Marco Gerlinger,Yinyin Yuan,Kenneth J. Pienta,Karen S. Anderson,Robert A. Gatenby,Charles Swanton,David Posada,Chung I. Wu,Joshua D. Schiffman,E. Shelley Hwang,Kornelia Polyak,Alexander R. A. Anderson,Joel S. Brown,Mel Greaves,Darryl Shibata +21 more
TL;DR: A framework for classifying tumours is proposed that holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour, and the Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions.
References
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Journal ArticleDOI
Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B.
Chuan-ju Liu,Chuan-ju Liu,Sulayman D. Dib-Hajj,Sulayman D. Dib-Hajj,M. Renganathan,M. Renganathan,Theodore R. Cummins,Theodore R. Cummins,Stephen G. Waxman,Stephen G. Waxman +9 more
TL;DR: It is shown that fibroblast growth factor homologous factor 1B binds to the C terminus of the cardiac voltage-gated sodium channel Nav1.5 and modulates the properties of the channel, the first report showing that interaction with a growth factor can modulate properties of a voltage- gated sodiumChannel.
Journal ArticleDOI
Establishment of Hindbrain Segmental Identity Requires Signaling by FGF3 and FGF8
TL;DR: It is shown that signaling from this region by two members of the FGF family of secreted proteins, FGF3 and FGF8, is required to establish correct segmental identity throughout the hindbrain and for subsequent neuronal development.
Journal ArticleDOI
Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis
Vaishali N. Patel,Sarah M. Knox,Karen M. Likar,Karen M. Likar,Colin A. Lathrop,Rydhwana Hossain,Siavash Eftekhari,John M. Whitelock,Michael Elkin,Israel Vlodavsky,Matthew P. Hoffman +10 more
TL;DR: Results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis.
Journal ArticleDOI
A Unique Family of Endothelial Cell Polypeptide Mitogens: The Antigenic and Receptor Cross-Reactivity of Bovine Endothelial Cell Growth Factor, Brain-derived Acidic Fibroblast Growth Factor, and Eye-derived Growth Factor-II
A B Schreiber,J Kenney,J Kowalski,Kenneth A. Thomas,Guillermo Giménez-Gallego,Mari Rios-Candelore,J Di Salvo,Barritault D,J Courty,Y Courtois +9 more
TL;DR: It is argued that ECGF, acidic FGF, and EDGF-II belong to a common family of polypeptide growth factors that are potentiated by the glycosaminoglycan, heparin.
Journal ArticleDOI
The involvement of heparan sulfate (HS) in FGF1/HS/FGFR1 signaling complex.
Zhengliang L. Wu,Lijuan Zhang,Lijuan Zhang,Tomio Yabe,Balagurunathan Kuberan,David L. Beeler,Andre Love,Andre Love,Robert D. Rosenberg,Robert D. Rosenberg +9 more
TL;DR: A mechanism for the FGF·FGFR signaling complex formation on cell membrane was proposed, where FGF and FGFR have their own binding sites on HS and a distinct ternary complex formation site is directly responsible for mitogenic activity.
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