title: Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12.
abstract: The NKG2 family of NK receptors includes activating and inhibitory members. With the exception of the homodimer-forming NKG2D, NKG2 receptors recognize the nonclassical MHC class I molecule HLA-E, and they can be subdivided into two groups: those that associate with and signal through DAP12 to activate cells, and those that contain an ITIM motif to promote inhibition. The function of NKG2 family member NKG2E is unclear in humans, and its surface expression has never been conclusively established, largely because there is no Ab that binds specifically to NKG2E. Seeking to determine a role for this molecule, we chose to investigate its expression and ability to form complexes with intracellular signaling molecules. We found that NKG2E was capable of associating with CD94 and DAP12 but that the complex was retained intracellularly at the endoplasmic reticulum instead of being expressed on cell surfaces, and that this localization was dependent on a sequence of hydrophobic amino acids in the extracellular domain of NKG2E. Because this particular sequence has emerged and been conserved selectively among higher order primates evolutionarily, this observation raises the intriguing possibility that NKG2E may function as an intracellular protein.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Gerasim A
authors.initials: GA
authors.lastname: Orbelyan
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Fangming
authors.initials: F
authors.lastname: Tang
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sally
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Jason
authors.initials: J
authors.lastname: Solus
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Bertrand
authors.initials: B
authors.lastname: Meresse
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637;
authors.forename: Cezary
authors.initials: C
authors.lastname: Ciszewski
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, Quebec H3T 1C5, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec H3T 1C5, Canada; and.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Grenier
authors.affiliation: Sainte-Justine Hospital Research Centre, Montreal, Quebec H3T 1C5, Canada; Department of Pediatrics, University of Montreal, Montreal, Quebec H3T 1C5, Canada; and.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.affiliation: Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143.
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637; bjabri@medicine.bsd.uchicago.edu.
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; C527062:KLRC3 protein, human; C497869:KLRD1 protein, human; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; C110546:TYROBP protein, human