The IFNAR1 subunit of the type I IFN receptor complex contains a functional nuclear localization sequence.
A nuclear localization sequence (NLS) in the type II interferon (IFN) IFN gamma, which is responsible for the nuclear translocation of both the ligand and the alpha-subunit (IFNGR1) of the receptor complex, has previously been characterized and its role in signaling examined in detail. We have now identified an NLS in the type I IFN receptor (IFNAR) common subunit IFNAR1 from humans and show that the human IFNAR1 subunit can translocate to the nucleus following human IFN beta stimulation. An NLS in human IFNAR1 is located in the extracellular domain of IFNAR1 within the sequence (382)RKIIEKKT (numbered for the precursor form). Nuclear import by the NLS functions in a conventional fashion requiring cytosolic import factors, is energy-dependent and inhibited by the prototypical NLS of the SV40 large T-antigen. These studies provide a mechanism for nuclear import of IFNAR1, as well as for type I IFN ligands, and a starting point for studying an alternate role for IFNAR1 in nuclear signaling within the type I IFN system.
Subramaniam
Prem S
PS
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA. prem@scripps.edu
Johnson
Howard M
HM
D021581:Active Transport, Cell Nucleus; D000255:Adenosine Triphosphate / Q000378:metabolism; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism; D005455:Fluorescent Antibody Technique; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000494:pharmacology; D007371:Interferon-gamma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008565:Membrane Proteins; D019913:Nuclear Localization Signals; D010798:Phycocyanin / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
D000952:Antigens, Polyomavirus Transforming; C507964:IFNAR1 protein, human; D007370:Interferon Type I; D008024:Ligands; D008565:Membrane Proteins; D019913:Nuclear Localization Signals; D021122:Protein Subunits; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C002497:allophycocyanin; D010798:Phycocyanin; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D007371:Interferon-gamma; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate