Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation.
Although growth factor receptors are generally thought to carry out their role in signal transduction at the cell surface, many of these transmembrane proteins translocate to the nucleus after ligand stimulation. Here, we show that the nuclear translocation of fibroblast growth factor receptor (FGFR)1 occurs via a mechanism distinct from classical nuclear import but dependent on importin beta, a component of multiple nuclear import pathways. Furthermore, we show that nuclear FGFR1 induces c-Jun and is involved in the regulation of cell proliferation. These data are the first description of a nuclear import pathway for transmembrane growth factor receptors and elucidate a novel signal transduction pathway from the cell surface to the nucleus.
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. jreilly@neurome.com
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D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002458:Cell Fractionation; D003847:Deoxyglucose / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015151:Immunoblotting; D028884:Karyopherins; D051379:Mice; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D000963:Antimetabolites; D004791:Enzyme Inhibitors; D028884:Karyopherins; D009687:Nuclear Proteins; D009840:Oligomycins; D016755:Proto-Oncogene Proteins c-jun; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; C048335:oligomycin B; D000255:Adenosine Triphosphate; D003847:Deoxyglucose