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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FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma.
TL;DR: The current review comprehensively focuses on the role of FGFR2 inhibition either alone or in combination with other targeted therapy that act on down-stream and alternate kinase pathways in cholangiocarcinoma.
Journal ArticleDOI
Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation.
Leah C. Biggs,Otto J. M. Mäkelä,Satu-Marja Myllymäki,Rishi Das Roy,Katja Närhi,Johanna Pispa,Tuija Mustonen,Marja L. Mikkola +7 more
TL;DR: Combining mouse models with 3D and 4D microscopy and RNAseq profiling indicate that dermal condensation occurs via directed cell movement and that Fgf20 orchestrates the early cellular and molecular events.
Journal ArticleDOI
Fgfr1 regulates development through the combinatorial use of signaling proteins
J. Richard Brewer,Andrei Molotkov,Pierre Mazot,Renée V. Hoch,Philippe Soriano,Philippe Soriano +5 more
TL;DR: Analysis of each mutant indicates that Frs2 binding to Fgfr1 has the most pleiotropic functions in development but also that the receptor uses multiple proteins additively in vivo, suggesting that Erk1/2-independent signaling pathways are functionally important for Fgf signaling in vivo.
Journal ArticleDOI
The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives.
TL;DR: Previous studies dealing with FGFR molecular aberrations, such as the gene amplification, point mutations, and chromosomal translocations that occur in breast cancer are recapitulated and the therapeutic usefulness of FGF/FGFR inhibitors is pointed out.
Journal ArticleDOI
The development, patterning and evolution of neural crest cell differentiation into cartilage and bone
TL;DR: This review focuses on the chondrogenic and osteogenic potential of cranial neural crest cells and discusses the roles of Sox9, Runx2 and Msx1/2 transcription factors and WNT, FGF and TGFβ signaling pathways in regulating neural crest cell differentiation into cartilage and bone.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,Hiroki Aizawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,Hitoshi Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Ryozo Nagai,Yo-ichi Nabeshima +16 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, and may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Makoto Kuro-o,Matsumura Yutaka,H. Arawa,Hiroshi Kawaguchi,Tatsuo Suga,Toshihiro Utsugi,Yoshio Ohyama,Masahiko Kurabayashi,Tadashi Kaname,Eisuke Kume,H. Iwasaki,Akihiro Iida,Takako Shiraki-Iida,Satoshi Nishikawa,Ryozo Nagai,Yo-ichi Nabeshima,K. Sharma,L. Kelly,T. Dandekar +18 more
TL;DR: A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes in the mouse, including short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema as mentioned in this paper.
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Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
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