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
Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.
TL;DR: It is demonstrated that Fgfr3 is essential for normal endochondral ossification and inner ear development and Contrasts between the skeletal phenotype and achondroplasia suggest that activation of FGFR3 causes achondaplasia.
Journal ArticleDOI
A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway
H. Kouhara,Y. R. Hadari,T Spivak-Kroizman,J Schilling,Dafna Bar-Sagi,Irit Lax,Joseph Schlessinger +6 more
TL;DR: It is found that FRS2 is myristylated and that this modification is essential for membrane localization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK activation.
Journal ArticleDOI
Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.
Andrew O.M. Wilkie,Andrew O.M. Wilkie,Sarah F. Slaney,Sarah F. Slaney,Michael Oldridge,Michael D. Poole,Geraldine J. Ashworth,Anthony D. Hockley,Richard Hayward,David J. David,L J Pulleyn,Paul Rutland,S. Malcolm,Robin M. Winter,William Reardon +14 more
TL;DR: Specific missense substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert syndrome are identified.
Journal ArticleDOI
Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer
Jonathan Weiss,Martin L. Sos,Danila Seidel,Martin Peifer,Thomas Zander,Johannes M. Heuckmann,Roland T. Ullrich,Roopika Menon,Sebastian Maier,Alex Soltermann,Holger Moch,Patrick Wagener,Florian Fischer,Stefanie Heynck,Mirjam Koker,Jakob Schöttle,Frauke Leenders,Franziska Gabler,Ines Dabow,Silvia Querings,Lukas C. Heukamp,Hyatt Balke-Want,Sascha Ansén,Daniel Rauh,Ingelore Baessmann,Janine Altmüller,Zoe Wainer,Matthew Conron,Gavin M. Wright,Prudence A. Russell,Ben Solomon,Elisabeth Brambilla,Christian Brambilla,Philippe Lorimier,Steinar Sollberg,Odd Terje Brustugun,Walburga Engel-Riedel,Corinna Ludwig,Iver Petersen,Jörg Sänger,Joachim H. Clement,Harry J.M. Groen,Wim Timens,Hannie Sietsma,Erik Thunnissen,Egbert F. Smit,Daniëlle A.M. Heideman,Federico Cappuzzo,C. Ligorio,Stefania Damiani,Michael Hallek,Rameen Beroukhim,William Pao,Bert Klebl,Matthias Baumann,Reinhard Buettner,Karen Ernestus,Erich Stoelben,Jürgen Wolf,Peter Nürnberg,Peter Nürnberg,Sven Perner,Roman K. Thomas +62 more
TL;DR: F focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
Journal ArticleDOI
Resolution of Cell Fate Decisions Revealed by Single-Cell Gene Expression Analysis from Zygote to Blastocyst
Guoji Guo,Mikael Huss,Guo Qing Tong,Chaoyang Wang,Li Li Sun,Neil D. Clarke,Paul Robson,Paul Robson +7 more
TL;DR: It is shown that in the morula, blastomeres coexpress transcription factors specific to different lineages, but by the 64-cell stage three cell types can be clearly distinguished according to their quantitative expression profiles.
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