A functional bipartite nuclear localisation signal in the cytokine interleukin‐5

FEBS Letters

Ford, Sally²  Gustin, Sonja E.²  Jans, Patricia¹  Briggs, Lyndall J.¹  Jans, David A.¹  Young, Ian G.² 

[1] Nuclear Signalling Laboratory, Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, A.C.T. 2601, Australia;Medical Molecular Biology Group, Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, A.C.T. 2601, Australia

关键词: Interleukin-5;    Nuclear protein import;    Confocal laser scanning microscopy;    Microinjection;    Cytokine receptor;    IL-5;    interleukin-5;    IL-3;    interleukin-3;    GM-CSF;    granulocyte macrophage colony stimulating factor;    JAK;    Janus kinase;    STAT;    signal transducer and activator of transcription;    NLS;    nuclear localisation sequence;    SFX;    6-(fluorescein-5-(and-6)-carboxamido)hexanoic acid;    succinimidyl ester;    IAF;    5-iodacetamido-fluorescein;    CLSM;    confocal laser scanning microscopy;   

DOI  :  10.1016/S0014-5793(97)00293-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown