Inhibition of the protein kinase C pathway promotes anti-CD95-induced apoptosis in Jurkat T cells

The present study was undertaken to investigate the role of the 5-hydroxytryptamine (5-HT) ionotrophic receptor 5-HT3 in the activation of human Jurkat T-cells. 5-HT and 2-methyl-5-HT (2Me-5-HT), an agonist of the 5-HT3 receptor, induced increases in intracellular free Na+ concentrations, [Na+]i, via opening of the ionotrophic receptor in these cells. These two serotonergic (5-hydroxytryptaminergic) agents potentiated phytohaemagglutinin (PHA)-induced T-cell activation. However, they failed to potentiate dioctanoglycerol-plus-ionomycin-stimulated T-cell blastogenesis. Interestingly, an inhibitor of protein kinase C (PKC), GF 109203X, curtailed significantly 5-HT and 2Me-5-HT-potentiated T-cell activation. These results demonstrate that the opening of the 5-HT3 ionotrophic receptor is implicated in T-cell activation via the PKC pathway. Furthermore, 5-HT and 2Me-5-HT stimulated phospholipase D (PLD) activity, as measured by the production of phosphatidylethanol and phosphatidylbutanol at the expense of phosphatidic acid (PA). GF 109203X significantly curtailed the 5-HT- and 2Me-5-HT-induced PLD activity and T-cell activation. The PLD/PA pathway stimulated by these two serotonergic agents resulted in the production of 1,2-diacylglycerol (DAG) mass in Jurkat T-cells. These results altogether suggest that 5-HT and 2Me-5-HT potentiate T-cell activation via increases in [Na+]i and the activation of the PKC-dependent PLD pathway.

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The Role of Protein Kinase C in TCR-Induced Interleukin-2 Secretion in Human Jurkat T Cells

Biochemical Society Transactions ◽

10.1042/bst021383s ◽

1993 ◽

Vol 21 (4) ◽

pp. 383S-383S

Author(s):

DAVID. H. WILLIAMS ◽

TREVOR. J. HALLAM ◽

EDWARD. J. MURRAY

Keyword(s):

T Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Interleukin 2 ◽

Jurkat T Cells ◽

Kinase C

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ROLE OF PROTEIN KINASE C IN CD47-MEDIATED PHOSPHATIDYLSERINE EXPOSURE PATHWAY BY BRIC126 IN JURKAT T CELLS.

Journal of Immunology and Clinical Microbiology ◽

10.5455/jicm.23.20170613 ◽

2017 ◽

pp. 1

Author(s):

IKENNA UCHENDU ◽

CHIDOZIE AGU ◽

OLIVER ORJI ◽

BLESSING CHEKWUBE ◽

TOCHI NWOSU

Keyword(s):

T Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Jurkat T Cells ◽

Kinase C ◽

Phosphatidylserine Exposure ◽

Exposure Pathway

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Protein Kinase C-θ Participates in NF-κB Activation Induced by CD3-CD28 Costimulation through Selective Activation of IκB Kinase β

Molecular and Cellular Biology ◽

10.1128/mcb.20.8.2933-2940.2000 ◽

2000 ◽

Vol 20 (8) ◽

pp. 2933-2940 ◽

Cited By ~ 196

Author(s):

Xin Lin ◽

Alison O'Mahony ◽

Yajun Mu ◽

Romas Geleziunas ◽

Warner C. Greene

Keyword(s):

T Cells ◽

Protein Kinase C ◽

Protein Kinase ◽

Interleukin 2 ◽

Cell Receptor ◽

Jurkat T Cells ◽

Necrosis Factor Alpha ◽

Kinase C ◽

Iκb Kinase ◽

Cd28 Costimulation

ABSTRACT The NF-κB/Rel family of eukaryotic transcription factors plays an essential role in the regulation of inflammatory, antiapoptotic, and immune responses. NF-κB is activated by many stimuli including costimulation of T cells with ligands specific for the T-cell receptor (TCR)-CD3 complex and CD28 receptors. However, the signaling intermediates that transduce these costimulatory signals from the TCR-CD3 and CD28 surface receptors leading to nuclear NF-κB expression are not well defined. We now show that protein kinase C-θ (PKC-θ), a novel PKC isoform, plays a central role in a signaling pathway induced by CD3-CD28 costimulation leading to activation of NF-κB in Jurkat T cells. We find that expression of a constitutively active mutant of PKC-θ potently induces NF-κB activation and stimulates the RE/AP composite enhancer from the interleukin-2 gene. Conversely, expression of a kinase-deficient mutant or antisense PKC-θ selectively inhibits CD3-CD28 costimulation, but not tumor necrosis factor alpha-induced activation of NF-κB in Jurkat T cells. The induction of NF-κB by PKC-θ is mediated through the activation of IκB kinase β (IKKβ) in the absence of detectable IKKα stimulation. PKC-θ acts directly or indirectly to stimulate phosphorylation of IKKβ, leading to activation of this enzyme. Together, these results implicate PKC-θ in one pathway of CD3-CD28 costimulation leading to NF-κB activation that is apparently distinct from that involving Cot and NF-κB-inducing kinase (NIK). PKC-θ activation of NF-κB is mediated through the selective induction of IKKβ, while the Cot- and NIK-dependent pathway involves induction of both IKKα and IKKβ.

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