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
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 novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.
Raffaella Richelda,Raffaella Richelda,Raffaella Richelda,Domenica Ronchetti,Domenica Ronchetti,Domenica Ronchetti,Luca Baldini,Luca Baldini,Luca Baldini,Lilla Cro,Lilla Cro,Lilla Cro,Luigi Viggiano,Luigi Viggiano,Luigi Viggiano,R. Marzella,R. Marzella,R. Marzella,Mariano Rocchi,Mariano Rocchi,Mariano Rocchi,Takemi Otsuki,Takemi Otsuki,Takemi Otsuki,Luigia Lombardi,Luigia Lombardi,Luigia Lombardi,Anna Teresa Maiolo,Anna Teresa Maiolo,Anna Teresa Maiolo,Antonino Neri,Antonino Neri,Antonino Neri +32 more
TL;DR: Findings indicate that the t(4; 14)(p16.3; q32) represents a novel, recurrent chromosomal translocation in MM, and suggest that the FGFR3 gene may be the target of this abnormality and thus contribute to tumorigenesis in MM.
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.
Journal ArticleDOI
FGF19-induced Hepatocyte Proliferation Is Mediated through FGFR4 Activation
Xinle Wu,Hongfei Ge,Bryan Lemon,Steven Vonderfecht,Jennifer Weiszmann,Randy Ira Hecht,Jamila Gupte,Todd Hager,Zhulun Wang,Richard A. Lindberg,Yang Li +10 more
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
Omar A. Ibrahimi,Anna V. Eliseenkova,Alexander N. Plotnikov,Kai Yu,David M. Ornitz,Moosa Mohammadi +5 more
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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