Heparan sulfate fibroblast growth factor receptor complex: Structure‐function relationships

  title={Heparan sulfate fibroblast growth factor receptor complex: Structure‐function relationships},
  author={Wallace L. Mckeehan and Mikio Kan},
  journal={Molecular Reproduction and Development},
  • W. Mckeehan, M. Kan
  • Published 1 September 1994
  • Biology, Chemistry
  • Molecular Reproduction and Development
Splice variations in genes coding for the transmembrane FGF receptor (FGFR) result in isoforms that vary in the ectodomain, intracellular juxtamembrane domain, and the intracellular kinase domain. An analysis of biochemical functions of distinct recombinant isoforms expressed in baculoviral‐infected insect cells allowed generation of models for function of splice variants in both the ecto‐ and intracellular domains. A structural model for the ectodomain of the FGFR is proposed as follows… 
The heparan sulfate-fibroblast growth factor family: diversity of structure and function.
Divalent Cations and Heparin/Heparan Sulfate Cooperate to Control Assembly and Activity of the Fibroblast Growth Factor Receptor Complex*
It is shown that the interaction of heparin with FGF ligands is not affected by divalent cations, and a model is proposed where doval cations and heparan sulfate cooperate to maintain FGFR in a conformation that restricts trans-phosphorylation between intracellular kinase domains.
The FGFR D3 domain determines receptor selectivity for fibroblast growth factor 21.
Molecular modeling studies on binding of bFGF to heparin and its receptor FGFR1.
The proposed structural properties of the proposed model of bFGF/heparin/FGFR1 complex are consistent with the binding mechanism of FGF to its receptor, the receptor dimerization, and the reported site-specific mutagenesis and biochemical cross-linking data.
Molecular Modeling and Deletion Mutagenesis Implicate the Nuclear Translocation Sequence in Structural Integrity of Fibroblast Growth Factor-1*
The results confirm that a primary role of the NYKKPKL sequence domain is to maintain the structural integrity of FGF-1 required for optimal binding to and activation of the heparan sulfate-transmembrane receptor complex.
Heparan sulfate is required for interaction and activation of the epithelial cell fibroblast growth factor receptor-2IIIb with stromal-derived fibroblast growth factor-7
Results suggest that, similar to other FGF polypeptides, heparan sulfate within the pericellular matrix is required for activity of FGF-7.
Isoforms of Receptors of Fibroblast Growth Factors
  • S. Gong
  • Biology
    Journal of cellular physiology
  • 2014
A better understanding of the diversity of FGF signaling in different developmental contexts and diseased states can be achieved through increased knowledge of the presence of specific FGFR isoforms and their impact on downstream signaling and functions.
Glycosaminoglycan affinity of the complete fibroblast growth factor family.
Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4.
FGF9 presents a unique case of ligand-receptor specificity and fulfills the criteria as a high affinity, heparin-dependent ligand for FGFR3.


An essential heparin-binding domain in the fibroblast growth factor receptor kinase.
The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand.
Fibroblast growth factor receptors from liver vary in three structural domains.
It is shown that changes in heparin-binding fibroblast growth factor gene expression and receptor phenotype occur during liver regeneration and in hepatoma cells, and three amino-terminal domain motifs combine to form a minimum of 6 and potentially 12 homologous polypeptides that constitute the growth factor receptor family in a single human liver cell population.
Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants.
The results suggest a mechanism for control of signal transduction by different concentrations of ligand through heterodimerization of combinatorial splice variants from the same receptor gene, and propose that complexes of phosphotyrosine 766 kinase monomers and SH2 domain signal transducers may constitute unactivated presignal complexes.
The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain.
The arrangement of exons and introns in the human FGF receptor 1 (FGFR 1) gene has been mapped and three alternative exons encoding a portion of the third immunoglobulin (Ig)-like domain of the receptor are found.
Receptor- and heparin-binding domains of basic fibroblast growth factor.
The results suggest the possibility of designing specific analogs of FGF that are capable of inhibiting the biological effects of FGRF, and specifically those that possess partial agonist activity and stimulate DNA synthesis when tested in the absence of exogenous FGF.
Identification of tyrosines 154 and 307 in the extracellular domain and 653 and 766 in the intracellular domain as phosphorylation sites in the heparin‐binding fibroblast growth factor receptor tyrosine kinase (flg)
Four tyrosine residues have been identified as phosphorylation sites in the tyrosin kinase isoform of the heparin‐binding fibroblast growth factor receptor flg (FGF‐R1), which was phosphorylated and fragmented with trypsin while immobilized on heparIn‐agarose beads.