Activation-induced upregulation of inhibitory killer Ig-like receptors is regulated by protein kinase C.
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.
Chwae
Yong-Joon
YJ
Department of Microbiology and Brain Korea 21 Project of Medical Sciences, Seoul, Korea.
Lee
Jae Myun
JM
Kim
Eun Joon
EJ
Lee
Seung Tae
ST
Soh
Jae-Won
JW
Kim
Jongsun
J
D000098:Acetophenones / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004789:Enzyme Activation; D005089:Exocytosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D019169:Jurkat Cells; D008247:Lysosomes / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
D000098:Acetophenones; D001578:Benzopyrans; D002227:Carbazoles; D007211:Indoles; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; C081021:Go 6976; C085746:rottlerin; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate