Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of T cell proliferation and differentiation into mature effector cells is dependent on two principal exogenous signals that are provided by the antigen or mitogen and IL2. The enzyme protein kinase C (PKC) has a major role in the antigen-receptor signalling pathway in T cells, but appears not to be involved in signalling via the IL2-receptor (IL2-R). Since both pathways trigger a series of sequentially coordinated transcriptional events in which numerous genes are activated, we tested whether a T cell mitogen acting via the TCR/CD3 complex, and IL2, affect the expression of the conventional, Ca(2+)-dependent, PKC genes (alpha, beta and gamma) in T cells. Stimulation of human peripheral blood lymphocytes or an enriched population of human T cells with phytohemagglutinin resulted in augmented mRNA levels of PKC alpha and PKC beta, but not PKC gamma-gene. The response peaked at 24-48 hr when a 3-5-fold increase was observed. Stimulation of IL2-R alpha-expressing T cells with human recombinant IL2 induced cell proliferation and transcription of the IL2-R alpha gene (greater than 100-fold), but did not change mRNA levels of PKC alpha or PKC beta genes. The results suggest that stimulation of human T cells with mitogens acting via the TCR/CD3 complex, that involve activation of PKC, is accompanied also by a late activation of selected PKC genes. By contrast, agonists such as IL2, that operate via a different signalling pathway, do not modify the expression of any of the known conventional PKC genes.
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PMID:Mitogen-induced human T cell proliferation is associated with increased expression of selected PKC genes. 163 62

DL-1,2-Dioctanoylglycerol (1,2-DiC8) added to human peripheral resting T lymphocytes was rapidly metabolized to produce octanoic acid and further to small molecules, probably by the action of diacylglycerol lipase and/or nonspecific esterase. Only a small portion was converted to the corresponding phosphatidic acid or was isomerized to 1,3-DiC8 before being metabolized. The uptake of 1,2-DiC8 by the cell was apparently fast, and the rate of disappearance of 1,2-DiC8 was dependent on the cell densities; at a higher density of T lymphocytes 1,2-DiC8 was removed quickly, whereas at a lower cell density 1,2-DiC8 remained for a longer period of time. With a fixed amount of 1,2-DiC8 added, the extent of interleukin 2 receptor alpha-subunit (IL-2R alpha) expression was inversely related to the cell density and proportional to the duration of exposure of the cells to 1,2-DiC8. Repeated doses of 1,2-DiC8 potentiated IL-2R alpha expression. In contrast, a single dose of phorbol 12-myristate 13-acetate caused T-lymphocyte activation to similar extents irrespective of the cell density, probably because the phorbol ester was not metabolized and remained in membranes. The available evidence supports a proposal made in a previous paper and indicates that the sustained activation of protein kinase C for at least the first 3-4 hr is essential for the activation of resting T lymphocytes.
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PMID:Metabolic rate of membrane-permeant diacylglycerol and its relation to human resting T-lymphocyte activation. 192 30