RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine.

RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Research Abstract Details 

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RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Abstract Text:

Randolph S Faustino,Lyle N W Stronger,Melanie N Richard,Michael P Czubryt,David A Ford,Michele A Prociuk,Elena Dibrov,Grant N Pierce,

The intracellular mechanism responsible for the mitogenic effects of lysophosphatidylcholine (LPC) is unclear. Import of proteins from the cytoplasm into the cell nucleus is integral to the regulation of gene expression and cell growth. We hypothesized that LPC exerts its intracellular effects through alterations in nuclear protein import. Rabbit aortic smooth muscle cells incubated with LPC induced a significant increase in cell proliferation in both quiescent cells (63.2+/-6.48% of control) and cells grown in 1% fetal bovine serum (FBS) (28.3+/-7.35% of control). Vascular smooth muscle cells were preincubated with LPC then microinjected with a marker protein for nuclear import. A significant stimulation of nuclear protein transport was observed. Using a conventional nuclear protein import assay in permeabilized cells, a significant stimulation of import (72.3+/-5.2% of control) was again observed when the cytosolic nuclear import cocktail was treated with LPC. This effect was not observed with other lysophosphatidyl species. LPC also activated the extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) pathway, and this was blocked by 2'-amino-3'-methoxyflavone (PD98059), which inhibits the activation of ERK 1/2. The stimulation of nuclear import was also blocked by PD98059. LPC-induced MAPK activation augmented GTP hydrolysis by RanGAP, a RanGTPase activating protein and a critical regulatory component of nuclear protein import, and this stimulation was again blocked by PD98059. We conclude that LPC alters gene expression and cell proliferation through striking effects on nuclear protein import via a MAP kinase-induced activation of RanGAP. This may play an important role in cancer and atherosclerosis and other disorders involving accelerated cell growth/proliferation.

RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Publishing Authors By Initials

RS Faustino,LN Stronger,MN Richard,MP Czubryt,DA Ford,MA Prociuk,E Dibrov,GN Pierce,

For similar animals: chordata: vertebrates: mammals: lagomorpha: rabbits research abstracts see: animals: chordata: vertebrates: mammals: lagomorpha: rabbits research

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RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular pharmacology

VOLUME: 71

Page Numbers: 438-45

Journal Abbreviation: Mol. Pharmacol.

ISSN: 0026-895X

DAY: 14

MONTH: 11

YEAR: 2006

RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Information

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LANGUAGE: eng

NlmUniqueID: 35623

RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Keywords Mesh Terms:

KEYWORDS: Rabbits

MESH TERMS: metabolism

Chemical & Substance for Abstract: RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine. Information

Substance Name: Mitogen-Activated Protein Kinase 3

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine.

AFFILIATION: Cell Biology Laboratory, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, 351 Tache Avenue, Winnipeg, Manitoba, Canada.

Country: United States

AGENCY: United States NCRR

GRANT: RR00954

ACRONYM: RR

MEDLINETA: Mol Pharmacol

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