Molecular Mechanisms of Fibroblast Growth Factor Signaling in Physiology and Pathology

被引：160

作者：

Belov, Artur A. ^{[1
]}

Mohammadi, Moosa ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

来源：

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY | 2013年 / 5卷 / 06期

关键词：

LIGAND-BINDING SPECIFICITY; RECEPTOR TYROSINE KINASE; DOMINANT HYPOPHOSPHATEMIC RICKETS; HEPARAN-SULFATE PROTEOGLYCANS; FACTOR HOMOLOGOUS FACTOR; INNER-EAR AGENESIS; C-TERMINAL TAIL; FGF RECEPTOR; CRYSTAL-STRUCTURE; STRUCTURAL BASIS;

D O I：

10.1101/cshperspect.a015958

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：24

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