AI Article Synopsis
- Fibroblast growth factors (FGFs) play a crucial role in various biological processes like development, tissue maintenance, and metabolism by signaling through FGF receptors (FGFRs), often aided by heparan sulfate (HS) or Klotho coreceptors.
- Recent structural and biophysical research has uncovered important mechanisms of FGF signaling, including how FGFs bind to receptors, the specifics of ligand-receptor interactions, and the regulation of kinases involved in the process.
- This understanding not only sheds light on how mutations in FGFRs can lead to diseases but also has potential implications for developing targeted therapies for a range of medical conditions.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660835 | PMC |
| http://dx.doi.org/10.1101/cshperspect.a015958 | DOI Listing |
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