Disease relevance of Prkcc

• We conclude that interventions that lead to hypertrophy of cardiomyocytes (phorbol esters, epinephrine, and endothelin-1) activate PKC-epsilon [1].
• The novel demonstration of elevated expression of PDGF-B and its induction by PKC activation identifies a potential new molecular step in the pathogenesis of diabetic retinopathy [2].
• The 5'-flanking region of protein kinase C (PKC) gamma gene was identified from a rat liver genomic library in a bacteriophage lambda Charon 4A [3].
• The authors conclude that during and after ischemia, PKC and CaMKII-alpha are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival [4].
• Chronic hyperammonemia alters differentially the intracellular distribution of PKC isoforms [5].

Psychiatry related information on Prkcc

• We conclude that the simultaneous inhibition of PI3K and PKC can induce GSK-3 overactivation, and further strengthen and prolong the Alzheimer-like tau hyperphosphorylation in N2a cells, suggesting the establishment of a cell model with early pathological events of Alzheimer's disease [6].
• Since RACK1 facilitates the PKC substrate accessibility, driving its cellular localization, the coordinate regulation of the PKC/RACK system by morphine could be a relevant molecular mechanism in opiate addiction [7].
• Thus, these results directly suggest that activation of PKC pathways in a specific hippocampal area alters rat auditory discrimination reversal learning [8].
• Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis [9].
• That similar patterns of PKC translocation are observed in experimental models of ischaemic preconditioning and genetic PKC manipulation provide evidence for a dose-dependent cardioprotective phenotype induced by physical activity [10].

High impact information on Prkcc

• These cell lines contain a 20- to 53-fold increase in PKC activity and exhibit dramatically enhanced morphologic changes following exposure to the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) [11].
• Thus, the mere overproduction of a single form of PKC is sufficient to confer multiple growth abnormalities in rat fibroblasts [11].
• Transfection of NIH 3T3 cells with plasmids containing rat brain protein kinase C-I (PKC-I) cDNA controlled by strong viral promoter/enhancer elements led to PKC-I gene expression as assessed by Northern analysis, cellular binding of phorbol ester, immunoblotting of cellular PKC, and membrane-associated PKC activity [12].
• The protein kinase C (PKC) family of serine/threonine kinases functions downstream of nearly all membrane-associated signal transduction pathways [13].
• Moreover, the pro-inflammatory peptide, bradykinin, and the putative endogenous ligand, anandamide, respectively induced and enhanced VR activity, in a PKC-dependent manner [14].

Chemical compound and disease context of Prkcc

• The role of protein kinase C (PKC) in tyrosine phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) following transient cerebral ischemia was investigated [15].
• Chronic hyperammonemia also affects differentially NMDA-induced translocation of PKC isoforms [5].
• The effects of hypoxia on protein kinase C (PKC) isozymes (alpha, beta I, beta II, and gamma) were examined in the hippocampus from rats subjected to hypoxic conditions (5% O2 in 95% N2) for 30 min in a chamber [16].
• To clarify the role of PKC in vasoconstrictor-stimulated VSMC production of bFGF and hypertrophy, PKC was down-regulated by prolonged exposure to PMA or was inhibited with calphostin C or staurosporine before the addition of TXA2 or Ang II [17].
• Intrathecal MK 801 (an NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a non-NMDA receptor antagonist), or GM1 ganglioside (an intracellular PKC inhibitor) treatment was given to examine the effects of these agents on the development and expression of thermal hyperalgesia in morphine-tolerant rats [18].

Biological context of Prkcc

• These results demonstrate that alternative splicing of the NR1 messenger RNA regulates its phosphorylation by PKC, and that mRNA splicing is a novel mechanism for regulating the sensitivity of glutamate receptors to protein phosphorylation [19].
• Here we demonstrate that PKC increases NMDA channel opening rate and delivers new NMDA channels to the plasma membrane through regulated exocytosis [20].
• In neurons, PKC induced a rapid delivery of functional NMDARs, assessed by electrophysiology, and an increase in NMDAR clusters on the surface of dendrites and dendritic spines, as indicated by immunofluorescence [20].
• These studies provide the first evidence of selective organ and tissue distributions of the calcium-independent PKC isoenzymes [21].
• An ANOVA showed that only C1 and no other exon or interaction of exons determined the degree of NMDAR current modulation by PKC [22].

Anatomical context of Prkcc

• PKC induced a rapid delivery of functional NMDARs to the cell surface and increased surface NR1 immunofluorescence in Xenopus oocytes expressing NMDARs [20].
• PKC epsilon was present in brain, kidney, and pancreas, whereas PKC epsilon' was present predominantly in brain [21].
• The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC-alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes [1].
• All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines) [1].
• We investigated the ET receptor subtype involved in mitogenic signaling in glomerular mesangial cells and the role of protein kinase C (PKC) and protein tyrosine kinase (PTK) activity [23].

Associations of Prkcc with chemical compounds

• PKC was sequentially purified from rat brain, and the calcium-dependent forms were finally resolved by hydroxyapatite chromatography [21].
• Serine residue 890 in the C1 cassette is a primary target of PKC phosphorylation and a critical residue in receptor clustering at the membrane [24].
• On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC-epsilon undergoes a rapid (< 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction [1].
• PKC-epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1 [1].
• The effects of high glucose and protein kinase C (PKC) activation on platelet-derived growth factor (PDGF)-BB and of ET-1 expression in the retina of streptozotocin (STZ)-induced diabetic rats and bovine retinal pericytes (BRPC) were examined [2].

Physical interactions of Prkcc

• Endothelin (1 x 10(-6) M) also increased the plasma membrane bound protein kinase C (PKC) activity by 4 fold [25].
• Taken together, our results indicate that PKC interacts in vivo with calreticulin and suggest that they can operate in common signalling pathways [26].

Enzymatic interactions of Prkcc

• The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890 [27].
• We now demonstrate that PKA and various PKC isoforms phosphorylate the NMDA receptor in vitro [28].
• These data demonstrate that TnI and C-protein are phosphorylated in myocardial cells by both PKA and PKC, resulting in different functional consequences in each case [29].
• Cytosolic PKC-dependent histone-phosphorylating enzyme activity and PKC-beta immunoreactivity of both adipocytes and soleus muscles increased progressively with age (or weight) in rats weighing less than 400 g [30].

Regulatory relationships of Prkcc

• Thus, PKC regulates NMDAR channel gating and trafficking in recombinant systems and in neurons, mechanisms that may be relevant to synaptic plasticity [20].
• These results indicate that p125FAK might play a role in a signal transduction system of ET-1 in glomerular mesangial cells and that the ET-1-induced tyrosine phosphorylation of p125FAK is largely dependent on the PKC pathway [31].
• Protein kinase C (PKC) inhibitor staurosporine inhibited ETs-induced ICAM-1 expression on both cell types [32].
• Activation of protein kinase C (PKC) can upregulate tooth eruption molecules such as osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF) [33].
• These results suggest that rPLD1 is a glycosylated protein and that it is negatively regulated by phosphorylation by PKC in vitro [34].

Other interactions of Prkcc

• PKC alpha, -beta and -gamma isoenzymes separated by hydroxylapatite chromatography all cross-reacted with anti-PKC zeta [35].
• A general PKC inhibitor, GF109203X, suppressed PDGF-BB's induction of ET-1 mRNA [2].
• A highly specific PKC beta inhibitor, LY379196, blocked dopamine efflux that was stimulated by either amphetamine or the PKC activator, 12-O-tetradecanoylphorbol-13-acetate [36].
• The purpose of this study was to identify the specific PKC isozymes mediating the effects of HG on MC extracellular signal-regulated protein kinase (ERK1/2) signaling and alpha1(IV) collagen expression in response to ET-1 [37].
• Therefore, we investigated the signaling pathway for Ca(2+)- and PKC-dependent NF-kappaB activation, inducible nitric-oxide synthase expression, and tumor necrosis factor-alpha (TNF-alpha) production in LPS-stimulated rat peritoneal macrophages [38].

Analytical, diagnostic and therapeutic context of Prkcc

• The PKC isoenzymes demonstrated a distinctive tissue distribution when evaluated by Western blot and immunocytochemistry [21].
• Because of our inability to detect PKC-alpha, -beta 1, -gamma, and -delta in whole extracts, PKC isotypes were partially purified from whole heart by DEAE Sepharose chromatography [1].
• This finding provides not only a rationale to explain the presence of multiple PKC family members, but also permits the dissection of the complex cellular signaling cascade involving PKC family members [39].
• The levels of protein kinase C-gamma (PKC-gamma ) and the calcium/calmodulin-dependent kinase II-alpha (CaMKII-alpha) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion [4].
• In the current study, immunocytochemistry was used to test whether the relationship between elevated PKC-gamma and memory impairment among aged rats could be localized further within regions of the hippocampus [40].

References