Inhibition of IL-2 receptor induction and IL-2 production in the human leukemic cell line Jurkat by a novel peptide inhibitor of protein kinase C.
We recently reported that the myristoylated peptide N-myristoyl-Lys-Arg-Thr-Leu-Arg (N-m-KRTLR) is a novel protein kinase C inhibitor. In this study, we investigated the biological effects of N-m-KRTLR using as an in vitro model the induction of the IL-2 receptor and IL-2 secretion by Jurkat cells in response to stimulation with 12-O tetradecanoylphorbol-13-acetate (TPA) plus phytohemagglutinin (PHA) and TPA plus OKT3 mAb. N-m-KRTLR significantly suppressed induction of the IL-2 receptor on the surface of the Jurkat cells by TPA plus either PHA or OKT3 mAb. Furthermore, N-m-KRTLR inhibited the production and release of IL-2 from cultured Jurkat cells stimulated with TPA plus either PHA or OKT3 mAb. Similarly, this peptide significantly inhibited the IL-2 production in normal human peripheral blood mononuclear cells in response to stimulation by TPA and PHA. In contrast, this peptide did not affect expression of the CD3 complex on the surface of the Jurkat cells either alone or in the presence of TPA or PHA. Furthermore, N-m-KRTLR did not interfere with the spontaneous proliferation of the Jurkat cells, and its effects on IL-2 secretion and IL-2 receptor expression in the Jurkat cells were evident without loss of cell viability. These results suggest that the novel protein kinase C inhibitor N-m-KRTLR may selectively inhibit certain activation pathways of Jurkat cells and indicate the usefulness of N-m-KRTLR in the analysis of discrete events in T cell activation.
Ioannides
C G
CG
Department of Gynecology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Freedman
R S
RS
Liskamp
R M
RM
Ward
N E
NE
O'Brian
C A
CA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D015458:Leukemia, T-Cell; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D016853:Muromonab-CD3; D009842:Oligopeptides / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016853:Muromonab-CD3; D009842:Oligopeptides; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; C062296:N-myristoyl-lysyl-arginyl-threonyl-leucyl-arginine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate