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

We have examined the localization of phospholipid/calcium-dependent protein kinase (protein kinase C) in thymoma cells, which were resected from a patient with myasthenia gravis. Upon stimulation with 4 micrograms/ml of concanavalin A (Con A) for 30 min, protein kinase C activity in the cytosolic fraction was increased from 7.44 pmol/min per 10(7) cells to 11.42 pmol/min per 10(7) cells. On the other hand, membrane-associated protein kinase C activity was decreased from 1.69 to 0.71 pmol/min per 10(7) cells. On the contrary, 10(-7) mol/l tetradecanoyl phorbol acetate (TPA) decreased cytosolic protein kinase C activity from 9.31 to 8.04 pmol/min per 10(7) cells, while membrane-associated protein kinase C activity was increased from 1.69 to 2.94 pmol/min per 10(7) cells. Several endogenous phosphorylated proteins (mol wt 20,000, 23,000) were observed as inferred by SDS-polyacrylamide gel electrophoresis. These findings indicated that Con A and TPA produce differential translocation of protein kinase C.
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PMID:Concanavalin A- or phorbol ester-induced translocation of protein kinase C in thymoma cells from a patient with myasthenia gravis. 335 48

4-aminopyridine (4AP) is a general blocker of voltage-dependent K+ channels. This pyridine derivative has also been shown to inhibit T cell proliferation, to modulate immune responses and to alleviate some of the symptoms associated with neurological disorders such as multiple sclerosis, myasthenia gravis and Alzheimer's disease. 4AP triggers a Ca2+ response in lymphocytes, astrocytes, neurons and muscle cells but little is known about the regulation of the 4AP response in these cells. We report that 4AP induced a non-capacitative transplasma membrane influx of Ca2+ in Jurkat T lymphocytes. The influx of Ca2+ was not affected by activation or inhibition of protein kinase A (PKA). In contrast, activation of protein kinase C (PKC) by phorbol myristyl acetate (PMA), mezerein or 1-oleoyl-2-acetyl-sn-glycerol (OAG) inhibited the influx of Ca2+ triggered by 4AP. The inhibitory effect of PKC could be prevented by prior exposure of the cells to the PKC inhibitor GF 109203X. Under these conditions, mezerein and OAG no longer inhibited the 4AP-dependent Ca2+ response. Inhibition of serine and threonine protein phosphatases PP1 and PP2A by treating the cells with calyculin A (CalA) reduced the Ca2+ response to 4AP. Okadaic acid (OA) had no effect, suggesting an involvement of PP1. A combination of CalA and OAG (or PMA) abolished the influx of Ca2+ induced by 4AP, adding further evidence to the importance of protein phosphorylation in the modulation of the 4AP response. Our data suggest that the transplasma membrane influx of Ca2+ triggered by 4AP in Jurkat T cells can be modulated by the opposite actions of PKC and protein serine and threonine phosphatase(s).
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PMID:Protein kinase C inhibits the transplasma membrane influx of Ca2+ triggered by 4-aminopyridine in Jurkat T lymphocytes. 1288 Sep 46

Cholinergic signaling and acetylcholinesterase (AChE) influence immune response and inflammation. Autoimmune myasthenia gravis (MG) is mediated by antibodies to the acetylcholine receptor and current therapy is based on anti-AChE drugs. MG is associated with thymic hyperplasia, showing signs of inflammation. The objectives of this study were to analyze the involvement of AChE variants in thymic hyperplasia. We found lower hydrolytic activities in the MG thymus compared with adult controls, accompanied by translocation of AChE-R from the cytoplasm to the membrane and increased expression of the signaling protein kinase PKC-betaII. To explore possible causal association of AChE-R changes with thymic composition and function, we used an AChE-R transgenic model and showed smaller thymic medulla compared with strain-matched controls, indicating that AChE-R overexpression interferes with thymic differentiation mechanisms. Interestingly, AChE-R transgenic mice showed increased numbers of CD4(+)CD8(+) cells that were considerably more resistant in vitro to apoptosis than normal thymocytes, suggesting possibly altered positive selection. We further analyzed microarray data of MG thymic hyperplasia compared with healthy controls and found continuous and discrete changes in AChE-annotated GO categories. Together, these findings show that modified AChE gene expression and properties are causally involved in thymic function and development.
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PMID:The thymic theme of acetylcholinesterase splice variants in myasthenia gravis. 1727 1

In order to determine whether antigen-specific T-cell activation by dendritic cells (DCs) is accelerated in thymuses exhibiting lymphofollicular hyperplasia (TLFH) among patients with early-onset myasthenia gravis (EOMG), we investigated the expression levels of phosphorylated protein kinase C (PKC)theta and the local relationship between the presence of phosphorylated PKCtheta and the homing receptor CD44 or CD83, a marker for mature DCs, in samples taken from EOMG patients with early improvement following thymectomy, in remnant thymuses from late-onset MG patients, and in non-MG control thymuses. Antigen-specific T-cell activation was markedly accelerated in TLFH from EOMG patients. Activated T cells and adjacent DCs appeared to be components of a CD44(high) cell population circulating from the blood to the thymus. Although there is no convincing evidence that thymectomy is of benefit in MG, in some EOMG patients with early improvement following thymectomy, blockade of CD44-associated circulation mechanisms is probably the cause for the early benefits of thymectomy and is a potential alternative to thymectomy.
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PMID:Antigen-specific T-cell activation in hyperplastic thymus in myasthenia gravis. 1747 66

BACKGROUND Myasthenia gravis (MG) is an autoimmune neurological disorder of neuromuscular junctions. In this study we established experimental autoimmune myasthenia gravis (EAMG) rat models to investigate the effects of AEB-071 (AEB), which is a specific inhibitor of protein kinase C that prevents T lymphocyte activation. MATERIAL AND METHODS We utilized animals divided into 4 groups: (1) control rats, (2) EAMG, (3) AEB-071+EAMG, and (4) AZP+EAMG. Drug treatment was continued for 10 days. Ten weeks after immunization we measured body weights, assessed mortality rates, and used Lennon scores to evaluate EAMG grades. We also assessed the proportions of Treg, Th1, Th2, Th17, and lymphocytes using flow cytometry. RESULTS In the absence of drug treatment, we found a significant decline in body weights in the EAMG group in comparison to control rats, and EAMG group rats also had higher Lennon scores (P<0.05). Interestingly, we found that AEB-071 restored the body weight of EAMG rats and the decreased mortality rate compared to AZP treatment. Although a decrease in the number of Treg cells was observed, the proportion of Th lymphocytes was significantly increased in the EAMG group, and AEB-071 treatment decreased the proportion of Th lymphocytes. CONCLUSIONS We concluded that AEB-071 treatment imparts beneficial effects in EAMG rat models by reducing mortality rate and restoring Th lymphocyte balance, and thus may be an attractive candidate for use in MG treatment.
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PMID:AEB-071 Ameliorates Muscle Weakness by Altering Helper T Lymphocytes in an Experimental Autoimmune Myasthenia Gravis Rat Model. 3292 May 88