title: Cytoplasmic targeting of the proto-oncogene SET promotes cell spreading and migration.
abstract: The RhoGTPase Rac1 is activated in a polarised fashion and controls cell motility. We previously showed that Rac1 binds the PP2A inhibitor SET and recruits nuclear SET to the cytosol. We show that a SET mutant, lacking a nuclear localization signal, SET(ΔNLS), promotes cell spreading and motility. This was accompanied by an increase in the number and frequency of membrane ruffles. Pharmacological inhibition of PP2A did not mimic the effects of SET(ΔNLS), however, we found that expression of SET and SET(ΔNLS) increases the levels of the MAP kinases ERK1 and ERK2.
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: B Daniel
authors.initials: BD
authors.lastname: Lam
authors.forename: Eloise C
authors.initials: EC
authors.lastname: Anthony
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
mesh_terms: D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D021961:Cell Membrane Structures / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D018613:Microscopy, Confocal; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C000715470:MAS1 protein, human; D050505:Mutant Proteins; D019913:Nuclear Localization Signals; D000090063:Proto-Oncogene Mas; C107953:RAC1 protein, human; D011993:Recombinant Fusion Proteins; C513473:SET protein, human; D014157:Transcription Factors; D054648:Protein Phosphatase 2; D020830:rac1 GTP-Binding Protein