PUBLICATION

Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development

Authors
Lightcap, C.M., Kari, G., Arias-Romero, L.E., Chernoff, J., Rodeck, U., and Williams, J.C.
ID
ZDB-PUB-090629-31
Date
2009
Source
PLoS One   4(6): e6025 (Journal)
Registered Authors
Chernoff, Jonathan
Keywords
Nuclear import, Zebrafish, Embryos, Dyneins, Breast cancer, Dimerization, Phosphorylation, Cell binding
MeSH Terms
  • Humans
  • Cytoplasmic Dyneins
  • Gene Expression Regulation, Neoplastic*
  • Protein Binding
  • Gene Expression Regulation, Developmental*
  • Active Transport, Cell Nucleus
  • Zebrafish
  • Animals
  • p21-Activated Kinases/metabolism
  • p21-Activated Kinases/physiology*
  • Dyneins/metabolism*
  • Dyneins/physiology*
  • Cell Line, Tumor
  • Cell Survival
  • Cell Movement
  • Dimerization
  • Binding Sites
(all 17)
PubMed
19557173 Full text @ PLoS One
Abstract
Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import of Pak1 in MCF-7 cells, and that this event is contingent upon LC8-mediated Pak1 dimerization. In contrast, Pak2, which lacks an LC8 binding site but contains a nuclear localization sequence identical to that in Pak1, remains cytoplasmic upon EGF stimulation of MCF-7 cells. Furthermore, we show that severe developmental defects in zebrafish embryos caused by morpholino injections targeting Pak are partially rescued by co-injection of wild-type human Pak1, but not by co-injection of mutant Pak1 mRNA disrupting either the LC8 binding or the NLS site. Collectively, these results suggest that LC8 facilitates nuclear import of Pak1 and that this function is indispensable during vertebrate development.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
WT + MO1-pak1standard conditionsDay 4
1 - 7 of 7
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zn1TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    pak1MO1-pak1MRPHLNO
    pak1MO2-pak1MRPHLNO
    1 - 2 of 2
    Show
    Fish
    Fish
    WT + MO1-pak1
    zn1Tg
    1 - 2 of 2
    Show
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    grcfpEFGgrcfp
    1 - 1 of 1
    Show
    Mapping
    No data available
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    Citation
    Lightcap, C.M., Kari, G., Arias-Romero, L.E., Chernoff, J., Rodeck, U., and Williams, J.C. (2009) Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development. PLoS One. 4(6):e6025.