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)

Protein kinase Cdelta (PKCdelta) is a widely expressed calcium-independent PKC isozyme that is induced at mRNA and protein levels upon stimulation of different cellular pathways. We found the rat PKCdelta gene to consist of 19 exons and to span approximately 29 kb. The exon-intron junctions follow the GT/AG rule. The 5' untranslated region is nearly 12 kb in length, and the transcription initiation site is surrounded by CG-rich sequences. The 5' flanking region contains putative binding sites for activator protein 1 (AP-1), nuclear factor kappa B (NFkappaB), stimulatory protein-1 (Sp-1) and nerve growth factor induced-C (NGFI-C) transcription factors. The PKCdelta gene is localized at the rat chromosome 19p14. The cloned gene will help to elucidate the role of PKCdelta in growth, differentiation and death of mammalian cells.
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PMID:Genomic structure and chromosomal localization of the rat protein kinase Cdelta-gene. 1072 3

1. In this study, the effect of 17beta-oestradiol on adenosine 3' : 5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase (PKA) activity was investigated. 2. Rapid (within 15 min) activation of basal PKA activity was observed in cytosolic fractions by 17beta-oestradiol but not by 17alpha-oestradiol, progesterone or testosterone. This stimulation was abolished by the specific PKA inhibitor PKI but not by the classical oestrogen receptor antagonist tamoxifen. 3. 17beta-Oestradiol did not stimulate basal PKA activity in membrane fractions or in cytosolic fractions from male rats. 4. The increase in cytosolic PKA activity was indirect as (i) it was inhibited by the adenylyl cyclase inhibitor SQ22536, (ii) it was mimicked by forskolin and (iii) 17beta-oestradiol did not cause a stimulation of basal PKA activity in either type I or type II commercially available PKA holoenzymes. 5. Protein kinase Cdelta (PKCdelta) was directly activated by 17beta-oestradiol. The specific PKC inhibitor, bisindolylmaleimide I (GF 109203X), abolished the 6. 17beta-oestradiol-induced PKA activation. 17beta-Oestradiol stimulate an increase in free intracellular calcium ion concentration ([Ca(2+)](i)) in isolated female but not male rat colonic crypts. This was inhibited by verapamil, nifedipine and zero extracellular [Ca(2+)] but unaffected by tamoxifen. 17alpha-Oestradiol, testosterone and progesterone failed to increase [Ca(2+)](i). 7. PKC and PKA inhibitors abolished the 17beta-oestradiol-induced increase in [Ca(2+)](i). 8. These results demonstrate the existence of a novel 17beta-oestradiol-specific PKA and Ca(2+) signalling pathway, which is both sex steroid- and gender-specific, in rat distal colonic epithelium.
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PMID:Rapid non-genomic activation of cytosolic cyclic AMP-dependent protein kinase activity and [Ca(2+)](i) by 17beta-oestradiol in female rat distal colon. 1074 93

Interleukin (IL-) 6 is closely related to gastrointestinal diseases. The question of whether gastric epithelial cell contributes to IL-6 production remains undefined. We aim to evaluate the regulatory pathway of IL-6 expression in gastric epithelial cells, by using different inflammatory cytokines, endotoxin, or protein kinase modulators. IL-6 was measured by ELISA. Phorbol-12-myristate-13-acetate (PMA), calcium ionophore A23187, TNF-alpha, IL-1beta, oncostatin M (OSM) but not lipopolysaccharide stimulated IL-6 production from gastric epithelial cell line MKN-28. Blocking protein tyrosine kinase (PTK) activation by herbimycin A or genistein, or blocking NF-kappaB activation by pyrrolidinedithiocarbamate, reduced the IL-6 expression induced by TNF-alpha, IL-1beta and OSM. Dexamethasone mimicked this effect. Protein kinase (PK) C inhibitor only reduced the PMA and OSM induced IL-6 production. Both inhibitors and activators for PKA and G-protein as well as IL-10 had no effects on IL-6 expression. These results indicate that inflammatory cytokines are crucial for IL-6 regulation in gastric epithelial cells. The IL-6 signal pathway is mediated through PTK, NF-kappaB, and also involve PKC, intracellular calcium and sensitive to dexamethasone, but is not related to PKA, G-protein and IL-10.
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PMID:Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28. 1088 Feb 63

Protein kinase (PK) C-zeta is implicated in the control of colonic epithelial cell proliferation in vitro. However, less is known about its physiological role in vivo. Using the transmissible murine colonic hyperplasia (TMCH) model, we determined its expression, subcellular localization, and kinase activity during native crypt hyperproliferation. Enhanced mitosis was associated with increased cellular 72-kDa holoenzyme (PKC-zeta, 3.2-fold), 48-kDa catalytic subunit (PKM-zeta, 3- to 9-fold), and 24-kDa membrane-bound fragment (M(f)-zeta, >10-fold) expression. Both PKC-zeta and PKM-zeta exhibited intrinsic kinase activity, and substrate phosphorylation increased 4.5-fold. No change in cellular PKC-iota/PKM-iota expression occurred. The subcellular distribution of immunoreactive PKC-zeta changed significantly: neck cells lost their basal subcellular pole filamentous staining, whereas proliferating cell nuclear antigen-positive cells exhibited elevated cytoplasmic, lateral membrane, and nuclear staining. Subcellular fractionation revealed increased PKC-zeta and PKM-zeta expression and activity within nuclei, which preferentially accumulated PKM-zeta. These results suggest separate cellular and nuclear roles, respectively, for PKC-zeta in quiescent and mitotically active colonocytes. PKM-zeta may specifically act as a modulator of proliferation during TMCH.
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PMID:Increased nuclear translocation of catalytically active PKC-zeta during mouse colonocyte hyperproliferation. 1089 66

Protein kinase Cdelta (PKCdelta) inhibits proliferation and decreases expression of the differentiation marker glutamine synthetase (GS) in C6 glioma cells. Here, we report that distinct, specific tyrosine residues on PKCdelta are involved in these two responses. Transfection of cells with PKCdelta mutated at tyrosine 155 to phenylalanine caused enhanced proliferation in response to 12-phorbol 12-myristate 13-acetate, whereas GS expression resembled that for the PKCdelta wild-type transfectant. Conversely, transfection with PKCdelta mutated at tyrosine 187 to phenylalanine resulted in increased expression of GS, whereas the rate of proliferation resembled that of the PKCdelta wild-type transfectant. The tyrosine phosphorylation of PKCdelta and the decrease in GS expression induced by platelet-derived growth factor (PDGF) were abolished by the Src kinase inhibitors PP1 and PP2. In response to PDGF, Fyn associated with PKCdelta via tyrosine 187. Finally, overexpression of dominant negative Fyn abrogated the decrease in GS expression and reduced the tyrosine phosphorylation of PKCdelta induced by PDGF. We conclude that the tyrosine phosphorylation of PKCdelta and its association with tyrosine kinases may be an important point of divergence in PKC signaling.
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PMID:Phosphorylation of protein kinase Cdelta on distinct tyrosine residues regulates specific cellular functions. 1094 93

Protein kinase Calpha (PKCalpha), which is known to be critical for the control of many cellular processes, was submitted to site-directed mutagenesis in order to test the functionality of several amino acidic residues. Thus, D187, D246 and D248, all of which are located at the Ca(2+) binding site of the C2 domain, were substituted by N. Subcellular fractionation experiments demonstrated that these mutations are important for both Ca(2+)-dependent and diacylglycerol-dependent membrane binding. The mutants are not able to phosphorylate typical PKC substrates, such as histone and myelin basic protein. Furthermore, using increasing concentrations of dioleylglycerol, one of the mutants (D246/248N) was able to recover total activity although the amounts of dioleylglycerol it required were larger than those required by wild type protein. On the other hand, the other mutants (D187N and D187/246/248) only recovered 50% of their activity. These data suggest that there is a relationship between the C1 domain, where dioleylglycerol binds, and the C2 domain, and that this relationship is very important for enzyme activation. These findings led us to propose a mechanism for PKCalpha activation, where C1 and C2 domains cannot be considered independent membrane binding modules.
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PMID:The C2 domain of protein kinase calpha is directly involved in the diacylglycerol-dependent binding of the C1 domain to the membrane. 1101 76

Protein kinase C (PKC) has been implicated in the sperm acrosome reaction. In the present study, we demonstrate induction of the acrosome reaction and activation of sperm PKCalpha by lysophosphatidic acid (LPA), which is known to induce signal transduction cascades in many cell types via binding to specific cell-surface receptors. Under conditions by which LPA activates PKCalpha, there is significant stimulation of the acrosome reaction, which is inhibited by PKC inhibitors. Protein kinase Calpha belongs to the Ca(2+)-dependent classical PKC family of isoforms, and indeed we show that its activation depends upon the presence of Ca(2+) in the incubation medium. Protein kinase Calpha is a known regulator of phospholipase D (PLD). We investigated the possible regulatory relationships between PKCalpha and PLD1. Using specific antibodies against PLD1, we demonstrate for the first time its presence in bovine sperm. Furthermore, PLD1 coimmunoprecipitates with PKCalpha and the PKCalpha-PLD1 complex decomposes after treatment of the cells with LPA or 12-O:-tetradecanoyl phorbol-13-acetate, resulting in the translocation of PKCalpha to the plasma membrane and translocation of PLD1 to the particulate fraction. A possible bilateral regulation of PKCalpha and PLD1 activation during the sperm acrosome reaction is suggested.
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PMID:Activation of protein kinase calpha in the lysophosphatidic acid-induced bovine sperm acrosome reaction and phospholipase D1 regulation. 1105 29

beta-Protein kinase (PKC) is essential for ligand-initiated assembly of the NADPH oxidase for generation of superoxide anion (O(2)). Neutrophils and neutrophilic HL60 cells contain both betaI and betaII-PKC, isotypes that are derived by alternate splicing. betaI-PKC-positive and betaI-PKC null HL60 cells generated equivalent amounts of O(2) in response to fMet-Leu-Phe and phorbol myristate acetate. However, antisense depletion of betaII-PKC from betaI-PKC null cells inhibited ligand-initiated O(2) generation. fMet-Leu-Phe triggered association of a cytosolic NADPH oxidase component, p47(phox), with betaII-PKC but not with RACK1, a binding protein for betaII-PKC. Thus, RACK1 was not a component of the signaling complex for NADPH oxidase assembly. Inhibition of beta-PKC/RACK1 association by an inhibitory peptide or by antisense depletion of RACK1 enhanced O(2) generation. Therefore, betaII-PKC but not betaI-PKC is essential for activation of O(2) generation and plays a positive role in signaling for NADPH oxidase activation in association with p47(phox). In contrast, RACK1 is involved in negative signaling for O(2) generation. RACK1 binds to betaII-PKC but not with the p47(phox).betaII-PKC complex. RACK1 may divert betaII-PKC to other signaling pathways requiring beta-PKC for signal transduction. Alternatively, RACK1 may sequester betaII-PKC to down-regulate O(2) generation.
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PMID:Roles for beta II-protein kinase C and RACK1 in positive and negative signaling for superoxide anion generation in differentiated HL60 cells. 1112 Jul 43

The role of regucalcin in the regulation of protein kinase activity in rat brain neuronal cells obtained from primary culture was investigated. Protein kinase activity was assayed using the 5500 g supernatant fraction of the cell homogenate. Protein kinase activity was significantly raised by the addition of calmodulin (5 microg/ml) or dioctanoylglycerol (5 microg/ml) in the presence of CaCl2 (10(-4) M), indicating that Ca2+/calmodulin-dependent protein kinase and protein kinase C is present in the neuronal cells. The addition of regucalcin (10(-9)-10(-7) M) in the enzyme reaction mixture caused a significant decrease in protein kinase activity in the absence of calmodulin or dioctanoylglycerol without Ca(2+) addition. Moreover, regucalcin completely prevented the activation of protein kinase by the addition of calmodulin or dioctonoylglyceral in the presence of CaCl(2) (10(-4) M). The presence of anti-regucalcin monoclonal antibody (25 or 50 ng/ml) caused a significant elevation of protein kinase activity without CaCl2 addition. Such an effect was significantly inhibited by the addition of trifluoperazine (2x10(-5) M), an antagonist of calmodulin, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The present study demonstrates that endogenous regucalcin in rat brain neuronal cells has an inhibitory effect on Ca2+ dependent protein kinase activity.
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PMID:Inhibitory role of regucalcin in the regulation of Ca2+ dependent protein kinases activity in rat brain neurons. 1116 91

Non-transformed rat intestinal epithelial cell (IEC) lines were used to study the action of 1,25-dihydroxyvitamin D(3) (1,25(OH)2D) in the intestine. The capacity of 1,25(OH)2D to increase the expression of the cytochrome P450 component of the vitamin D 24-hydroxylase (CYP24) was determined in IEC-6 and IEC-18 cell lines. In IEC-6 cells, which are derived from crypt cells isolated from the whole small intestine, 1,25(OH)2D markedly increased expression of CYP24 protein and mRNA within 12 h. In contrast, in IEC-18 cells, which are derived from crypt cells from the ileum only, 1,25(OH)2D did not increase expression of CYP24 until 24-48 h. The maximal levels of CYP24 mRNA seen in the IEC-18 cells were only 31% of the maximal levels seen in the IEC-6 cells. In the presence of 1,25(OH)2D, phorbol esters rapidly increased CYP24 mRNA levels in IEC-18 cells from almost undetectable to levels seen in IEC-6 cells. Protein kinase inhibitors abolished the stimulation by 1,25(OH)2D and by phorbol esters in both cell lines. Stimulation of mRNA levels by phorbol esters required new protein synthesis but stimulation by 1,25(OH)2D did not. These studies demonstrated that the rapid action of 1,25(OH)2D in IEC-6 cells is related to the activation of protein kinase C, an event which is missing in the IEC-18 cells. This differential response to 1,25(OH)2D probably takes place at a post-receptor site, since the number of vitamin D receptors in each cell line was found to be similar.
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PMID:Differential responsiveness of intestinal epithelial cells to 1,25-dihydroxyvitamin D3--role of protein kinase C. 1125 Jun 55


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