Nuclear localization of a complex of fibroblast growth factor(FGF)-1 and an NH2-terminal fragment of FGF receptor isoforms R4 and R1 α in human liver cells

Shuju Feng, Jianming Xu, Fen Wang, Mikio Kan, Wallace L. McKeehan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 (FGFR1α) 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.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1310
Issue number1
DOIs
StatePublished - Jan 10 1996

Keywords

  • Alternate splicing
  • Monoclonal antibody
  • Receptor metabolism
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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