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Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport

Sang-Oh Yoon1, Sejeong Shin, Yuzhen Liu

  • 1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Molecular Cell
|February 19, 2008
PubMed

Insights

Cell signaling pathways like Ras/ERK and PI3-kinase (PI3K) impact cell fate. This study reveals how RSK and Akt regulate nuclear transport by affecting RanBP3, linking these pathways to cell fate decisions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ras/ERK and PI3-kinase (PI3K) pathways are crucial for cellular responses.
  • Cell fate decisions are influenced by signal strength, timing, spatial location, and cellular context.
  • Nuclear transport's role in cell fate is significant, but its regulation by major signaling pathways is poorly understood.

Purpose of the Study:

  • To investigate the interplay between nuclear transport and the Ras/ERK/RSK and PI3K/Akt signaling pathways.
  • To elucidate how these signaling pathways regulate nuclear transport processes.
  • To understand the molecular mechanisms linking nuclear transport to cell fate determination.

Main Methods:

  • Investigated the downstream effectors RSK and Akt.
  • Analyzed the modulation of the Ran gradient and nuclear transport.
  • Examined the interaction, phosphorylation, and regulation of Ran-binding protein 3 (RanBP3) function.

Main Results:

  • RSK and Akt, activated downstream of Ras/ERK and PI3K respectively, were shown to modulate the Ran gradient.
  • These kinases were found to regulate nuclear transport by interacting with, phosphorylating, and controlling RanBP3.
  • Established a functional link between these key signaling pathways and nuclear transport regulation.

Conclusions:

  • RSK and Akt play a critical role in regulating nuclear transport.
  • The findings highlight a significant connection between nuclear transport and the Ras/ERK/RSK and PI3K/Akt signaling cascades.
  • This research provides new insights into the molecular mechanisms governing cell fate decisions.

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