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- Title
Effects of mitogen-activated protein kinases on nuclear protein import.
- Authors
Faustino, Randolph S.; Rousseau, Delphine C.; Landry, Melanie N.; Kostenuk, Annette L.; Pierce, Grant N.
- Abstract
ERK-2 MAP kinase activation induces inhibitory effects on nuclear protein import in vascular smooth muscle cells. The mechanism and characteristics of this effect of ERK-2 were investigated. An unusual dose-dependent effect of ERK-2 on nuclear protein import was identified. At higher concentrations (1 μg/mL) of ERK-2, nuclear protein import was stimulated, whereas lower concentrations (0.04 μg/mL) inhibited import. Intermediate concentrations exerted intermediate effects. The stimulatory and inhibitory effects at the 2 different ERK-2 concentrations were observed in both conventional, permeabilized cell assays of nuclear protein import and with in situ microinjection of smooth muscle cells. The biphasic effects of ERK-2 on import were also found for the other 2 members of the MAPK family, p38 and JNK. RanGAP was identified by structural analysis as a candidate target protein responsible for mediating the effects of ERK-2. After pretreatment with high concentrations of ERK-2, RanGAP activity was significantly increased by ~50%. In contrast, low concentrations of ERK-2 significantly attenuated RanGAP activity. These results demonstrate that all 3 members of the MAPK family can alter nuclear protein import in opposite directions depending upon the concentration of ERK-2 used. RanGAP represents the MAP kinase target whereby nuclear transport can be stimulated or inhibited.
- Subjects
MUSCLE cells; IMPORTS; MICROINJECTIONS; MITOGEN-activated protein kinases; CELL proliferation; CELL growth
- Publication
Canadian Journal of Physiology & Pharmacology, 2006, Vol 84, Issue 3/4, p469
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/Y05-131