title: Evidence that the intracellular domain of FGF receptor 2IIIb affects contact of the ectodomain with two FGF7 ligands.
abstract: Models of the oligomeric FGF signaling complex, including those derived from crystal structures, vary in stoichiometry and arrangement of the three subunits comprised of heparin/heparan sulfate chains, FGFR tyrosine kinase and activating FGF. Here, using covalent affinity crosslinking of radiolabeled FGF7 to binary complexes of FGFR2IIIb and heparin, we show that two molecules of FGF7 contact each FGFR2IIIb. This supports models that propose a dimeric complex of two units with stoichiometry 1 FGF:1 FGFR in which each FGF contacts both FGFR. The bivalent FGF7 contact was dependent on the full-length amino terminus of FGF7alpha and the intracellular domain of FGFR2IIIb extending through the juxtamembrane domain and the beta1 and beta2 strands of the kinase which is required for ATP binding. We propose that the differences in crosslinking report differences in relationships among subunits in the ectodomain of the complex that are affected by the amino terminus of FGF and the FGFR intracellular domain. From this, we suggest the corollary that conformational relationships among subunits in the ectodomain are transmitted to the intracellular and ATP binding domains during activation of the complex.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University and Center for Cancer Biology and Nutrition, Houston, Texas 77030-3303, USA.
authors.forename: F
authors.initials: F
authors.lastname: Uematsu
authors.forename: J H
authors.initials: JH
authors.lastname: Jang
authors.forename: M
authors.initials: M
authors.lastname: Kan
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: W L
authors.initials: WL
authors.lastname: McKeehan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors