title: Effects of mitogen-activated protein kinases on nuclear protein import.
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 microg/mL) of ERK-2, nuclear protein import was stimulated, whereas lower concentrations (0.04 microg/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 approximately 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.
authors.affiliation: Cell 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.
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Faustino
authors.forename: Delphine C
authors.initials: DC
authors.lastname: Rousseau
authors.forename: Melanie N
authors.initials: MN
authors.lastname: Landry
authors.forename: Annette L
authors.initials: AL
authors.lastname: Kostenuk
authors.forename: Grant N
authors.initials: GN
authors.lastname: Pierce
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D020928:Mitogen-Activated Protein Kinases / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D009687:Nuclear Proteins; D011994:Recombinant Proteins; D020928:Mitogen-Activated Protein Kinases