Klera1 – A Member of the NKR-P1 Family

NK cell receptors are heterodimers that can either initiate FcR-initiated or natural cytotoxicity (121). Most NKR-P1 members possess signaling motifs that activate Syk, leading to cell apoptosis or Src family and PI3K kinase activation of downstream effectors; however, some do not contain such motifs and instead regulate cytotoxicity via inhibition of signaling cascade (123).

Klera1 encodes one member of this family. To identify it further, The Miller lab performed screening with 10/78 or 3.2.3 antibodies on an Nkrp1 cDNA library from rats; then sequence analysis revealed two groups, known as NKR-P1A or P1B depending on whether their ability to inhibit NK cytotoxicity was FcRi dependent, suggesting they may serve different functions (43).

Klra1 forms functional heterodimers with its partner genes Klri1 and Klri2, in 293T cells, to identify infected or neoplastic targets by surface expression or co-immunoprecipitation as monomer or oligomer in NK cells. Furthermore, these heterodimers form in vivo where they bind to and internalize ligands which indicates their co-stimulatory as well as co-inhibitory properties.

Updated high-resolution maps of the Nkrp1/Klrb1 and Clr/Clec2 receptor-ligand systems on mouse chromosome 6 are shown here. Both genes, the Nkrp1 receptor gene (official gene nomenclature: Klrb1) and Clr ligand gene (official gene nomenclature: Clec2), are shown with their orientation (triangle direction), known or suspected function (triangle color) and intron-exon structure (vertical exon lines). Other select NK receptor genes located telomeric to CKD9 (blue) or Cd69 (red), are also shown here.