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
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
Thomas Lundåsen,Mary C. Hunt,Lisa-Mari Nilsson,Sabyasachi Sanyal,Bo Angelin,Bo Angelin,Stefan E.H. Alexson,Mats Rudling,Mats Rudling +8 more
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 (FGF) 21 Signaling through FGF Receptor (FGFR) 1c and FGFR3c
Masashi Suzuki,Yuriko Uehara,Kaori Motomura-Matsuzaka,Junko Oki,Yoshinori Koyama,Miho Kimura,Masahiro Asada,Akiko Komi-Kuramochi,Syuichi Oka,Toru Imamura +9 more
TL;DR: It is suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion.
Journal ArticleDOI
βKlotho Is Required for Fibroblast Growth Factor 21 Effects On Growth and Metabolism
Xunshan Ding,Jamie Boney-Montoya,Bryn M. Owen,Angie L. Bookout,Katie C. Coate,David J. Mangelsdorf,Steven A. Kliewer +6 more
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.
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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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