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
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Dissertation
Synthetic Physiology: Manipulating and Measuring Biological Pattern Formation With Light
TL;DR: The ability to spatially pattern morphogen signals in the embryo, and to map the complete transcriptional response of a system to a given signal, could enable the pressure-testing of mutually consistent morphogen models which may be obscured by the complexity of the embryo in vivo.
Quantifying the effects of hydrostatic pressure on fibroblast growth factor-2 binding by the human endothelium
TL;DR: Novel insight is provided regarding the involvement of FGF-2 signaling and interstitial pressure changes in various microvascular physiological and pathobiological processes.
Journal ArticleDOI
FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma
Maria Pia Tamburello,Barbara Altieri,Iuliu Sbiera,Sandra Sigala,Alfredo Berruti,Martin Fassnacht,Silviu Sbiera +6 more
TL;DR: A review of the role of the FGF/FGFR system in both organogenesis and tumorigenesis can be found in this article , where a dual role of FGF and FGFR is discussed.
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Role of the N‐Terminal Transmembrane Helix Contacts in the Activation of FGFR3
TL;DR: In this paper, generalized replica exchange with solute tempering method was applied to wild type (WT) and G380R mutant (G380R) of FGFR3, and the simulation results were in good agreement with the solid-state nuclear magnetic resonance (NMR) spectroscopy.
Journal ArticleDOI
The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in Xenopus.
Fangfang Zhang,Xuechen Zhu,Pan Wang,Qing He,Huimei Huang,Tianrui Zheng,Yongyu Li,Hong Jia,Linping Xu,Huaxiang Zhao,Gabriele Colozza,Qinghua Tao,Edward M. De Robertis,Yi Ding +13 more
Abstract: Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in Xenopus embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in Xenopus embryos. fam3b messenger RNA (mRNA) is initially expressed maternally and uniformly in the early Xenopus embryo and then in the epidermis at neurula stages. Overexpression of Xenopus fam3b mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of fam3b by specific antisense morpholino oligonucleotides in Xenopus resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In Xenopus embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in Xenopus embryos and may provide molecular insights into FAM3B-associated human diseases.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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