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Molecular mechanism of the activation-induced cell death inhibition mediated p70 inhibitory killer cell Ig-like receptor in Jurkat T cells

 Yong Joon Chwae  ;  Mi Jung Chang  ;  Sang Myun Park  ;  Ho Yoon  ;  Hyun Joo Park  ;  Se Jong Kim  ;  Jongsun Kim 
 JOURNAL OF IMMUNOLOGY, Vol.169(7) : 3726-3735, 2002 
Journal Title
Issue Date
Amino Acid Sequence ; Apoptosis/drug effects ; Apoptosis/genetics ; Apoptosis/immunology* ; Cytoplasm/chemistry ; Cytoplasm/enzymology ; Cytoplasm/genetics ; Cytoplasm/immunology ; Diglycerides/pharmacology ; Fas Ligand Protein ; Humans ; Ionomycin/pharmacology ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/metabolism ; Jurkat Cells ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Ligands ; Lymphocyte Activation*/drug effects ; Lymphocyte Activation*/genetics ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/biosynthesis ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Membrane Proteins/pharmacology ; Molecular Sequence Data ; Peptide Fragments/genetics ; Peptide Fragments/immunology ; Peptide Fragments/pharmacology ; Phosphatidylserines/pharmacology ; Phytohemagglutinins/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/metabolism ; Protein Kinase C-alpha ; Protein Kinase C-theta ; Receptors, Immunologic/biosynthesis ; Receptors, Immunologic/genetics ; Receptors, Immunologic/physiology* ; Receptors, KIR ; Receptors, KIR3DL1 ; Recombinant Proteins/pharmacology ; T-Lymphocytes/cytology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology* ; T-Lymphocytes/metabolism* ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection ; fas Receptor/metabolism
In this study we investigated the molecular mechanism of the activation-induced cell death (AICD) inhibition mediated by a p70 inhibitory killer cell Ig-like receptor (KIR3DL1, also called NKB1) in Jurkat T cells. Using stable Jurkat transfectants that express KIR or CD8-KIR fusion proteins we have shown for the first time that KIR inhibits, in a ligation-independent manner, the AICD induced by PHA, PMA/ionomycin, or anti-CD3 Ab. The AICD inhibition mediated by KIR appears to result from the blockade of Fas ligand induction upon activation of the Jurkat transfectants. Moreover, the membrane-proximal 20 aa of the KIR cytoplasmic tail were determined to play a crucial role in this process. Since the membrane-proximal portion of the KIR cytoplasmic tail contains a putative protein kinase C (PKC) substrate site, we investigated the molecular interaction between KIR and PKC. Immunoprecipitation analysis demonstrated that KIR constitutively bound both to PKCα, a conventional Ca2+-dependent PKC, and to PKCθ, a novel Ca2+-independent PKC. Furthermore, an in vitro kinase assay revealed that PKC activation was blocked after PHA stimulation in Jurkat transfectants expressing KIR. These observations were supported by the finding that a recombinant KIR cytoplasmic tail also appeared to inhibit PKCα activation in vitro. Taken together these data strongly suggest that KIR inhibits the AICD of T cells by blocking Fas ligand induction upon stimulation, in a process that seems to be accomplished by PKC recruitment to the membrane-proximal PKC binding site and subsequent inhibition of PKC activation against the activating stimuli.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
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