Molecular mechanisms of fibroblast growth factor signaling in physiology and pathology

Fibroblast growth factors (FGFs) signal in a paracrine or endocrine fashion to mediate a myriad of biological activities, ranging from issuing developmental cues, maintaining tissue homeostasis, and regulating metabolic processes. FGFs carry out their diverse functions by binding and dimerizing FGF...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in biology 2013-06, Vol.5 (6), p.a015958-a015958
Main Authors: Belov, Artur A, Mohammadi, Moosa
Format: Article
Language:English
Subjects:
Alternative Splicing
Dimerization
Fibroblast Growth Factors - chemistry
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - metabolism
Humans
Models, Biological
Models, Molecular
Mutation - genetics
Phosphorylation
Protein Conformation
Receptor Protein-Tyrosine Kinases - metabolism
Receptors, Fibroblast Growth Factor - chemistry
Receptors, Fibroblast Growth Factor - genetics
Receptors, Fibroblast Growth Factor - metabolism
Signal Transduction - physiology
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Summary:Fibroblast growth factors (FGFs) signal in a paracrine or endocrine fashion to mediate a myriad of biological activities, ranging from issuing developmental cues, maintaining tissue homeostasis, and regulating metabolic processes. FGFs carry out their diverse functions by binding and dimerizing FGF receptors (FGFRs) in a heparan sulfate (HS) cofactor- or Klotho coreceptor-assisted manner. The accumulated wealth of structural and biophysical data in the past decade has transformed our understanding of the mechanism of FGF signaling in human health and development, and has provided novel concepts in receptor tyrosine kinase (RTK) signaling. Among these contributions are the elucidation of HS-assisted receptor dimerization, delineation of the molecular determinants of ligand-receptor specificity, tyrosine kinase regulation, receptor cis-autoinhibition, and tyrosine trans-autophosphorylation. These structural studies have also revealed how disease-associated mutations highjack the physiological mechanisms of FGFR regulation to contribute to human diseases. In this paper, we will discuss the structurally and biophysically derived mechanisms of FGF signaling, and how the insights gained may guide the development of therapies for treatment of a diverse array of human diseases.
ISSN:1943-0264
1943-0264
DOI:10.1101/cshperspect.a015958