Activation-induced upregulation of inhibitory killer Ig-like receptors is regulated by protein kinase C

Abstract

Inhibitory killer Ig-like receptor (KIR) expression was upregulated by protein kinase C (PKC) activation in stable Jurkat clones that express KIR or CD8KIR fusion proteins. PKC-induced KIR upregulation was mediated by the cytoplasmic tail of KIR and regulated at the post-transcriptional level. PKC inhibition, metabolic labeling and colocalization studies demonstrated that the activation of the conventional PKCs upregulated surface and cellular KIR levels by stimulating the maturation processes in endoplasmic reticulum-Golgi and by promoting the recycling of surface KIR through sorting endosomes. Similar studies also revealed that KIR was secreted to plasma membrane through lytic granules in a PKCdelta-dependent manner. Consequently, PKCdelta inhibition caused the formation of giant perinuclear granules, which trapped KIR and FasL as well as CPE and Lamp1.