FUNCTIONAL COUPLING OF NKR-P1 RECEPTORS TO VARIOUS HETEROTRIMERIC G-PROTEINS IN RAT INTERLEUKIN-2-ACTIVATED NATURAL-KILLER-CELLS

NKR-P1 molecules constitute a family of type II membrane receptors in natural killer (NK) cells that preferentially activate NK cell killing and release of interferon-gamma from these cells. Here, we demonstrat e that anti NKR-P1 enhances GTP binding in rat interleukin-2- activate d NK cell membranes; GTP binding to G(i3)alpha, G(s) alpha, G(q,11)alp ha and G(z) alpha increased noticeably in these cell membranes after t reatment with anti-NKR-P1. Western blot analysis of membrane proteins prepared from interleukin-2-activated NK cells reveals the presence of G(i1,2)alpha, G(i3)alpha, G(o) alpha, G(s) alpha, G(q,11)alpha, G(z) alpha, and G(12)alpha, but not G(13)alpha. However, only alpha(i3), al pha(s), alpha(q,11), and alpha(z), but not alpha(i1,2), alpha(o), alph a(12), or alpha(13) subunits when immunoprecipitated with the appropri ate anti-G protein antibodies, are associated with NKR-P1 when immunob lotted with anti-NKR-P1. Reciprocally, NKR-P1 immunoprecipitated with anti-NKR-P1 is associated with alpha(i3), alpha(s), alpha(q,11), and a lpha(z) immunoblotted with anti-G proteins. These results are the firs t to demonstrate the physical and functional coupling of NKR-P1 to the heterotrimeric G proteins in NK cells.