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Effects of mitogen-activated protein kinases on nuclear protein import

Randolph S Faustino1, Delphine C Rousseau, Melanie N Landry

  • 1Cell Biology Laboratory, Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculties of Medicine and Pharmacy, University of Manitoba, Winnipeg, Canada.

Canadian Journal of Physiology and Pharmacology
|August 12, 2006
PubMed

Insights

Extracellular signal-regulated kinase 2 (ERK-2) exhibits a dual effect on nuclear protein import in smooth muscle cells. Depending on concentration, ERK-2 can either stimulate or inhibit this crucial cellular process by targeting RanGAP.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Nuclear protein import is vital for cellular function.
  • Mitogen-activated protein kinases (MAPKs) are key signaling molecules.
  • ERK-2's role in nuclear transport in vascular smooth muscle cells is not fully understood.

Purpose of the Study:

  • To investigate the mechanism and characteristics of ERK-2's effect on nuclear protein import.
  • To determine if the effect is dose-dependent.
  • To identify the target protein mediating these effects.

Main Methods:

  • Utilized permeabilized cell assays and in situ microinjection.
  • Examined the effects of varying ERK-2 concentrations.
  • Performed structural analysis to identify target proteins.
  • Assessed RanGAP activity.

Main Results:

  • ERK-2 demonstrated a biphasic effect: stimulation at high concentrations (1 microg/mL) and inhibition at low concentrations (0.04 microg/mL).
  • Similar biphasic effects were observed for p38 and JNK MAPKs.
  • RanGAP was identified as a key target, with its activity modulated by ERK-2 concentration.
  • High ERK-2 increased RanGAP activity by ~50%, while low ERK-2 attenuated it.

Conclusions:

  • MAPK family members (ERK-2, p38, JNK) can oppositely regulate nuclear protein import based on concentration.
  • RanGAP is a critical mediator of MAPK-induced changes in nuclear transport.
  • This finding reveals a novel regulatory mechanism for nuclear transport in vascular smooth muscle cells.

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