Nuclear localization of a complex of fibroblast growth factor(FGF)-1 and an NH2-terminal fragment of FGF receptor isoforms R4 and R1alpha in human liver cells

Biochim Biophys Acta. 1996 Jan 10;1310(1):67-73. doi: 10.1016/0167-4889(95)00146-8.


FGF ligands and FGF receptor 1 (FGFR1) appear associated with the nucleus in addition to their extracellular and transmembrane locations. After receptor-dependent internalization in liver cells, radiolabeled 16-kDa FGF-1 appears in a 40-kDa covalent complex with a cellular protein. In this report, we show that in a human hepatoma cell line, HepG2, which expresses both FGFR4 and FGFR1, the 40-kDa complex cross-reacts with antibodies against the ectodomain of both types of receptors. In addition to antibody against FGF-1, a polyclonal antiserum against the three immunoglobulin (Ig)-like loop ectodomain of FGFR4 and a monoclonal antibody to a 19-residue sequence in the NH2-terminus of the NH2-terminal Ig Loop I of the three loop splice variant of FGFR1 (FGFR1alpha) reacts with the complex. A monoclonal antibody against an epitope in FGFR1 downstream of the inter-loop I/II sequence which reacts with intact FGFR1 failed to cross-react with the 40-kDa complex. Cell fractionations and indirect immunofluorescent localization revealed that the 40-kDa complex associates with the particulate fraction of cells, particularly the nucleus and associated cytoskeletal elements. We propose that the NH2-terminal Ig-loop of the three loop isoforms of FGFR, which are generally associated inversely with cell growth, may play a role at or in the nucleus in addition to modification of affinity of the FGFR ectodomain for heparan sulfate and FGF ligand.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies / immunology
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytoskeleton / metabolism
  • Epitopes / analysis*
  • Epitopes / immunology
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Fluorescent Antibody Technique
  • Humans
  • Liver / metabolism*
  • Liver / ultrastructure
  • Receptor Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / immunology
  • Receptors, Fibroblast Growth Factor / metabolism*


  • Antibodies
  • Epitopes
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • FGFR1 protein, human
  • FGFR4 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 4