title: A functional bipartite nuclear localisation signal in the cytokine interleukin-5.
abstract: Interleukin (IL)-5 is central in regulating eosinophilia in allergic disease and parasitic infections. We have identified a bipartite nuclear localisation signal (NLS) within amino acids 95-111 of human IL-5 (hIL-5), also present in mouse IL-5 (mIL-5). hIL-5 and mIL-5 were labelled fluorescently, and nuclear uptake subsequent to membrane binding and internalisation by intact receptor expressing cells visualised and quantified using confocal laser scanning microscopy. hIL-5 and mIL-5 were shown to be transported to the nucleus in in vivo and in vitro nuclear protein import assays. The hIL-5 NLS was able to target a heterologous protein to the nucleus both in vivo and in vitro. Mutations within the proximal arm of the NLS abrogated nuclear targeting activity, confirming its bipartite nature. The results imply a nuclear signalling role for IL-5 additional to pathways linked to the membrane receptor system.
authors.affiliation: Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.
authors.forename: D A
authors.initials: DA
authors.lastname: Jans
authors.forename: L J
authors.initials: LJ
authors.lastname: Briggs
authors.forename: S E
authors.initials: SE
authors.lastname: Gustin
authors.forename: P
authors.initials: P
authors.lastname: Jans
authors.forename: S
authors.initials: S
authors.lastname: Ford
authors.forename: I G
authors.initials: IG
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D015848:Interleukin-5 / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D015848:Interleukin-5; D009687:Nuclear Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011993:Recombinant Fusion Proteins