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Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation.

Reilly JF, Maher PA - J. Cell Biol. (2001)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. jreilly@neurome.com

ABSTRACT
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.

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ATP depletion induces the nuclear translocation of importin β. Cells were untreated or subjected to ATP depletion by treatment with oligomycin B and 2-deoxyglucose for the indicated times, in the absence or presence of FGF-2. Cells were separated into cytosolic (C) and nuclear (N) fractions, and equal amounts of protein were immunoblotted for importin β.
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Figure 3: ATP depletion induces the nuclear translocation of importin β. Cells were untreated or subjected to ATP depletion by treatment with oligomycin B and 2-deoxyglucose for the indicated times, in the absence or presence of FGF-2. Cells were separated into cytosolic (C) and nuclear (N) fractions, and equal amounts of protein were immunoblotted for importin β.

Mentions: Importin β is a critical component of multiple nuclear import pathways (Nakielny and Dreyfuss 1999). Recently, it was reported that microinjected importin β accumulates in the nucleus of ATP-depleted cells, whereas export of importin β from the nucleus is energy-dependent (Kose et al. 1999), characteristics similar to those of FGFR1. To determine if importin β is involved in the nuclear import of FGFR1, we first examined the localization of endogenous importin β in ATP-depleted cells. In untreated cells and cells treated with FGF-2, importin β was localized almost exclusively in the cytosol. Depletion of ATP resulted in a progressive nuclear accumulation of importin β, and this effect was potentiated by FGF-2 (Fig. 3). These data are consistent with a model in which energy is required to export importin β from the nucleus. In the ATP-depleted state, importin β that enters the nucleus during endogenously occurring transport fails to be exported. The potentiation of importin β nuclear accumulation by FGF-2 suggests that importin β plays a role in the nuclear import of FGFR1. Alternatively, since activation of FGF-induced signaling pathways results in the nuclear translocation of transcription factors such as NF-κB (Byrd et al. 1999), importin β may accumulate in the nucleus of ATP-depleted, FGF-2–treated cells after import of NLS-bearing cargoes.


Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation.

Reilly JF, Maher PA - J. Cell Biol. (2001)

ATP depletion induces the nuclear translocation of importin β. Cells were untreated or subjected to ATP depletion by treatment with oligomycin B and 2-deoxyglucose for the indicated times, in the absence or presence of FGF-2. Cells were separated into cytosolic (C) and nuclear (N) fractions, and equal amounts of protein were immunoblotted for importin β.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199207&req=5

Figure 3: ATP depletion induces the nuclear translocation of importin β. Cells were untreated or subjected to ATP depletion by treatment with oligomycin B and 2-deoxyglucose for the indicated times, in the absence or presence of FGF-2. Cells were separated into cytosolic (C) and nuclear (N) fractions, and equal amounts of protein were immunoblotted for importin β.
Mentions: Importin β is a critical component of multiple nuclear import pathways (Nakielny and Dreyfuss 1999). Recently, it was reported that microinjected importin β accumulates in the nucleus of ATP-depleted cells, whereas export of importin β from the nucleus is energy-dependent (Kose et al. 1999), characteristics similar to those of FGFR1. To determine if importin β is involved in the nuclear import of FGFR1, we first examined the localization of endogenous importin β in ATP-depleted cells. In untreated cells and cells treated with FGF-2, importin β was localized almost exclusively in the cytosol. Depletion of ATP resulted in a progressive nuclear accumulation of importin β, and this effect was potentiated by FGF-2 (Fig. 3). These data are consistent with a model in which energy is required to export importin β from the nucleus. In the ATP-depleted state, importin β that enters the nucleus during endogenously occurring transport fails to be exported. The potentiation of importin β nuclear accumulation by FGF-2 suggests that importin β plays a role in the nuclear import of FGFR1. Alternatively, since activation of FGF-induced signaling pathways results in the nuclear translocation of transcription factors such as NF-κB (Byrd et al. 1999), importin β may accumulate in the nucleus of ATP-depleted, FGF-2–treated cells after import of NLS-bearing cargoes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. jreilly@neurome.com

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus