Chemokines, G Proteins and Natural Killer Cells

Natural killer (NK) cells are anti-tumor and anti-viral effector cells. Members of C, CC, CXC and CX3C chemokines induce the chemotaxis and enhance the cytotoxicity of NK cells, suggesting that these cells express receptors for chemokines. The ability of members of chemokines to inhibit the replication of HIV-1 strains, combined with the ability of the same chemokines to activate the anti-viral NK cells, provide compelling evidence for the role of NK cells in eradicating HIV-1 infection. In addition, chemokines induce various intracellular signaling pathways in NK cells, which include activation of the heterotrimeric, and perhaps the small guanine nucleotide binding (G) proteins, as well as the mobilization of intracellular calcium, among other activities. Further, chemokines induce the phosphorylation of chemokine receptors through the recruitment of G protein-coupled receptor kinases (GRKs) resulting in the desensitization and turning off the signals. In this review, I will update the knowledge of the effect of chemokines on NK cell motility and the signal transduction pathways induced by chemokines in these cells.