klrf 1

Killer cell lectin-like receptor subfamily F member 1 (KLRF1) is known as NKp80. Human NKp80, a member of the C-type lectin family of proteins (1 - 3), is 231 aa in length with a 38 amino acid (aa) cytoplasmic region, a 21 aa transmembrane region, and a 172 aa extracellular domain (ECD). The protein strongly expressed in peripheral blood leukocytes and spleen, with weaker expression in lymph node and adult liver, and no expression detected in bone marrow, thymus, and fetal liver. Its' function involved in the natural killer (NK)-mediated cytolysis of PHA-induced lymphoblasts.

NKp80, also known as KLRF1, is an activating homodimeric C-type lectin-like receptor that is expressed on nearly all-natural killer cells and stimulates their cytotoxicity and cytokine release. NKp80 stimulates cytotoxicity upon engagement of its genetically linked ligand: myeloid-specific CTLR activation-induced C-type lectin (AICL). NKp80, but not NKp80 mutated at tyrosine 7 (NKp80/Y7F), is tyrosine phosphorylated. Accordingly, NKp80/Y7F, but not NKp80/Y3F or NKp80/Y37F, failed to induce cytotoxicity. NKp80 phosphopeptides comprising the Hemi-ITAM-like sequence surrounding tyrosine 7 bound Lck- and Syk-family kinases; accordingly, cross-linking of NKp8, but not NKp80/Y7F, induced Syk phosphorylation. Moreover, inhibition of Syk kinase, but not ZAP-7 kinase, impaired cytotoxic responses through NKp80. Atypical residues in the Hemi-ITAM-like motif of NKp80 cause an altered stoichiometry of phosphorylation but did not substantially affect NK cytotoxicity. Altogether, these results show that NKp80 uses an atypical Hemi-ITAM and Syk kinase to trigger cellular cytotoxicity.

NKp80, an activating homodimeric C-type lectin-like receptor (CTLR), is expressed on essentially all human natural killer (NK) cells and stimulates their cytotoxicity and cytokine release.