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 melanocortin-3 receptor, MC3-R, is abundant in the brain and is activated by gamma-2-melanocyte stimulating hormone (gamma-2-MSH). We have previously reported the translocation of protein kinase C (PKC) in spontaneous hypertensive rat (SHR) brain synaptosomes treated with gamma-2-MSH. In this study, the expression of PKA and the related PKB in SHR brain synaptosomes was analyzed. PKA was detected in total synaptosomal fractions but not in particulate fractions, whereas PKB was not detected in either fraction. We next tested the hypothesis that the PKC pathway is involved in MC3-R signaling in a neuronal, CAD, cell line. Mobilization of intracellular Ca2+ was analyzed by dual fluorescence imaging of Fura-2AM loaded MC3-R transfected cells. An increase in intracellular Ca2+ was observed upon treatment with gamma-2-MSH. A MC3-R-green fluorescent protein (GFP) fusion protein was expressed and shown to localize mainly to the plasma membrane in the soma and to neurites in differentiated CAD cells. Treatment with gamma-2-MSH led to a punctate appearance and co-immunoprecipitation of the receptor fusion protein with protein kinase C-gamma (PKC-gamma). Differentiation of some neuronal cells has been shown to be associated with changes in the expression levels of protein kinase C isoenzymes. Induction of CAD cell differentiation was associated with down-regulation of the atypical PKC-zeta and protein kinase B (PKB/Akt1), that was less pronounced in MC3-R transfected cells. However, the levels of classical PKC isozymes, PKC-alpha, PKC-gamma, and PKC-beta were unchanged. These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation.
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PMID:Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways. 1290 38

Ischemic preconditioning affords the most powerful protection to a heart submitted to a prolonged ischemia-reperfusion. During the past decade, a huge amount of work allowed to better understand the features of this protective effect as well as the molecular mechanisms. Ischemic preconditioning reduces infarct size and improves functional recovery; its effects on arrhythmias remain debated. Triggering of the protection involves cell surface receptors that activate pro-survival pathways including protein kinase C, PI3-kinase, possibly Akt and ERK1/2, whose downstream targets remain to be determined. Much attention has been recently focused on the role of mitochondrial K(+)ATP channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury. Based on these experimental studies attempts have been made to transfer preconditioning from bench to bedside. Human experimental models of ischemic preconditioning have been set up, including cardiac surgery, coronary angioplasty or treadmill exercise, to perform pathophysiological studies. Yet, protecting the heart of CAD (coronary artery disease) patients requires a pharmacological approach. The IONA trial has been an example of the clinical utility of preconditioning. It helped to demonstrate that chronic administration of nicorandil, a K(+)ATP opener that mimics ischemic preconditioning in experimental preparations, improves the cardiovascular prognosis in CAD patients. Recent experimental studies appear further encouraging. It appears that "postconditioning" the heart (i.e. performing brief episodes of ischemia-reperfusion at the time of reperfusion) is as protective as preconditioning. In other words, a therapeutic intervention performed as late as at the time of reflow can still significantly limit infarct size. Further work is needed to determine whether this may be transferred to the clinical practice.
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PMID:[How to use the paradigm of ischemic preconditioning to protect the heart?]. 1519 Apr 69

Akt promotes cell survival through phosphorylation. The physiological functions of cytoplasmic Akt have been well defined, but little is known about the nuclear counterpart. Employing a cell-free apoptotic assay and NGF-treated PC12 nuclear extracts, we purified Ebp1 as a factor, which contributes to inhibition of DNA fragmentation by CAD. Depletion of Ebp1 from nuclear extracts or knockdown of Ebp1 in PC12 cells abolishes the protective effects of nerve growth factor, whereas overexpression of Ebp1 prevents apoptosis. Ebp1 (S360A), which cannot be phosphorylated by PKC, barely binds Akt or inhibits DNA fragmentation, whereas Ebp1 S360D, which mimics phosphorylation, strongly binds Akt and suppresses apoptosis. Further, phosphorylated nuclear but not cytoplasmic Akt interacts with Ebp1 and enhances its antiapoptotic action independent of Akt kinase activity. Moreover, knocking down of Akt diminishes the antiapoptotic effect of Ebp1 in the nucleus. Thus, nuclear Akt might contribute to suppressing apoptosis through interaction with Ebp1.
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PMID:Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase. 1664 37

The multifunctional protein CAD initiates de novo pyrimidine biosynthesis in mammalian cells. CAD is activated by MAP kinase (Erk1/2) just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. MAP kinase phosphorylates Thr456, while PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. LC/mass spectrometry showed that Ser1873, a residue that lies within a putative protein kinase C (PKC) consensus sequence is also phosphorylated. Purified CAD was reacted with ATP and a panel of eight PKC isozymes. Most isozymes resulted in limited CAD phosphorylation, but the delta and epsilon isozymes were most effective. While the level of Thr456 phosphorylation is very low in confluent cells, exposure of stationary BHK 165-23 cells to the PKC activator, phorbol 12-myristate-13-acetate (PMA) resulted in a 3-fold increase in the modification of this residue. The stimulation of Thr456 phosphorylation was blocked by PKC inhibitors. The PKA inhibitor, H-89, also stimulated PMA-induced Thr456 modification probably because PKA mediated phosphorylation of CAD Ser1406 antagonizes the MAP kinase phosphorylation. Thus, the extent of Thr456 phosphorylation and the activation of pyrimidine biosynthesis depend on the synergistic and antagonistic interactions of three signaling pathways, MAP kinase, PKC and PKA. Deletions mutants lacking the putative PKC site, Ser1873 do not exhibit PMA induced Thr456 phosphorylation. We conclude that the activating MAP kinase phosphorylation of CAD proceeds through a PKC dependent pathway.
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PMID:Protein kinase C modulates the up-regulation of the pyrimidine biosynthetic complex, CAD, by MAP kinase. 1748 45