Human NKG2F is expressed and can associate with DAP12.
The NKG2 family of C-lectin type molecules is important for regulating the function of natural killer and subpopulations of T cells. NKG2A/B contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and accordingly functions as an inhibitory receptor, whereas NKG2C and -E/H associate with DAP12 via a positively charged residue in their transmembrane domains and function as activation receptors. Each of these molecules is paired with CD94 for expression and recognizes HLA-E as a ligand. NKG2F is an orphan gene within the NKG2 family whose translated product would contain both a positively charged residue in its transmembrane region, an intracellular ITIM-like sequence and an extracellular domain (62 residues) that is truncated relative to other NKG2 molecules. We show that NKG2F is expressed as a protein in NK cells. Expression appears to be confined to intracellular compartments probably due to its inability to associate with CD94. It can however associate with DAP12 thereby providing activation signaling potential. We were unable to demonstrate phosphorylation of the Tyr residue in the ITIM-like motif suggesting that it is a mock ITIM. NKG2F could be a receptor component with an as yet unidentified partner(s), could function to regulate cell activation through competition for DAP12 with other receptors, such as NKG2C and -E/H, or it could simply be a vestigial gene product.
Kim
Dae-Ki
DK
Receptor Cell Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Dr, Rockville, MD 20852, USA.
Kabat
Juraj
J
Borrego
Francisco
F
Sanni
Tolib B
TB
You
Chi-Hyun
CH
Coligan
John E
JE
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C527066:KLRC4 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C110546:TYROBP protein, human