The Protein Kinase C Family: Heterogeneity and Its Implications

Kikkawa, Ushio; Kishimoto, Akira; Nishizuka, Yasutomi

doi:10.1146/annurev.bi.58.070189.000335

Cited by 719 publications

(259 citation statements)

References 59 publications

(101 reference statements)

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“…In view of the distinctly higher reactivity of HNE towards thiol compared to amino groups [12], the formation of increased adduct between PKC thiol groups and HNE can also be assumed to occur in hemozoin-fed monocytes. PKC possesses important thiol groups that must be in the reduced state for correct functioning of the enzyme [23][24][25]. Thus, blockage of histidine/lysine amino groups as well as alkylation of thiol groups due to HNE/PKC adduct formation may lead to PKC inhibition, and explain the inhibition of purified PKC by micromolar concentrations of HNE observed here.…”

Section: Discussionmentioning

confidence: 95%

Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

et al. 1996

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Section: Discussionmentioning

confidence: 95%

Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

et al. 1996

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“…These findings prompted us to examine whether MG induces HB-EGF mRNA, by activating PKC to produce intracellular peroxides. RASMC were preincubated with 50 nM TPA for 24 h, during which protein kinase C is down-regulated by persistent treatment with TPA (41). The cells were further incubated with 400 M MG for 6 h or 5 mM 3-DG or with 50 nM TPA for 30 min.…”

Section: Involvement Of Reactive Oxygen Species In Mg or 3-dginduced mentioning

confidence: 99%

Selective Induction of Heparin-binding Epidermal Growth Factor-like Growth Factor by Methylglyoxal and 3-Deoxyglucosone in Rat Aortic Smooth Muscle Cells

Che

Asahi

Takahashi

et al. 1997

Journal of Biological Chemistry

103

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Methylglyoxal (MG) and 3-deoxyglucosone (3-DG), reactive dicarbonyl metabolites in the glyoxalase system and glycation reaction, respectively, selectively induced heparin-binding epidermal growth factor (HB-EGF)-like growth factor mRNA in a dose-and time-dependent manner in rat aortic smooth muscle cells (RASMC). A nuclear run-on assay revealed that the dicarbonyl may regulate expression of HB-EGF at the transcription level. The dicarbonyl also increased the secretion of HB-EGF from RASMC. However, platelet-derived growth factor, another known growth factor of smooth muscle cells (SMC), was not induced by both dicarbonyls. The dicarbonyl augmented intracellular peroxides prior to the induction of HB-EGF mRNA as judged by flow cytometric analysis using 2 ,7 -dichlorofluorescin diacetate. N-Acetyl-L-cysteine and aminoguanidine suppressed both dicarbonyl-increased HB-EGF mRNA and intracellular peroxide levels in RASMC. DL-Buthionine-(S,R)-sulfoximine increased the levels of 3-DG-induced HB-EGF mRNA. Furthermore, hydrogen peroxide alone also induced HB-EGF mRNA in RASMC. These results indicate that MG and 3-DG induce HB-EGF by increasing the intracellular peroxide levels. In addition, the pretreatment with 12-O-tetra-decanoylphorbol-13-acetate failed to alter dicarbonyl-induced HB-EGF mRNA expression in RASMC, suggesting that the signal transducing mechanism is not mediated by protein kinase C. Since HB-EGF is known as a potent mitogen for smooth muscle cells and is abundant in atherosclerotic plaques, the induction of HB-EGF by MG and 3-DG, as well as the concomitant increment of intracellular peroxides, may trigger atherogenesis during diabetes.Methylglyoxal (2-oxopropanal; MG), 1 a reactive ␣,␤-dicarbonyl metabolite and physiological substrate for the glyoxalase system (1), is formed by the non-enzymatic and enzymatic elimination of phosphate from dihydroxyacetone phosphate, glyceraldehyde-3-phosphate (2, 3), and by the oxidation of hydroxyacetone and aminoacetone (4 -6). The estimated rate of formation of methylglyoxal in tissues of normal healthy subjects is approximately 125 M/day which can largely be accounted for as a result of fragmentation of triose phosphates (2). The glyoxalase system, using reduced glutathione as a cofactor, catalyzes the conversion of methylglyoxal to D-lactate via the intermediate S-D-lactoylglutathione. The formation of methylglyoxal in cultured human red blood cells is increased under hyperglycemic conditions and by the addition of fructose,

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“…In many cell types, treatment with PMA for 12-18 h ablates the effects of acute PMA addition; under most circumstances, this is due to extensive proteolytic degradation of PKC (28). To determine whether this same phenomenon occurred in Jurkat cells, cells were treated for 18 h with 250 nM PMA, and the effects of acute PMA addition on stimulated changes in [Ca 2ϩ ] i were examined.…”

Section: Effects Of Phorbol Ester On Agonist-induced Changes Inmentioning

confidence: 99%

A Role for Protein Kinase CβI in the Regulation of Ca2+ Entry in Jurkat T Cells

Haverstick¹,

Dicus²,

Resnick³

et al. 1997

Journal of Biological Chemistry

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T cell activation leading to cytokine production and cellular proliferation involves a regulated increase and subsequent decrease in the intracellular concentration of Ca 2؉ ([Ca 2؉ ] i ). While much is understood about agonist-induced increases in [Ca 2؉ ] i , less is known about down-regulation of this pathway. Understanding the mechanism of this down-regulation is critical to the prevention of cell death that can be the consequence of a sustained elevation in [Ca 2؉ ] i . Protein kinase C (PKC), activated by the diacylglycerol produced as a consequence of T cell receptor engagement, has long been presumed to be involved in this down-regulation, although the precise mechanism is not wholly clear. In this report we demonstrate that activation of PKC by phorbol esters slightly decreases the rate of Ca 2؉ efflux from the cytosol of Jurkat T cells following stimulation through the T cell receptor or stimulation in a receptorindependent manner by thapsigargin. On the other hand, phorbol ester treatment dramatically reduces the rate of Ca 2؉ influx following stimulation. Phorbol ester treatment is without an effect on Ca 2؉ influx in a different T cell line, HSB. Down-regulation of PKC␤I expression by 18-h phorbol ester treatment is associated with a loss of the response to acute phorbol ester treatment in Jurkat cells, suggesting that PKC␤I may be the isozyme responsible for the effects on Ca 2؉ influx. Electroporation of an anti-PKC␤I antibody, but not antibodies against PKC␣ or PKC␥, led to an increase in the rate of Ca 2؉ influx following stimulation. Taken together, these data suggest that PKC␤I may be a component of the down-regulation of increases in [Ca 2؉ ] i associated with Jurkat T cell activation.Activation of T lymphocytes via stimulation through the T cell receptor for antigen (TCR) 1 leading to proliferation, cytokine production, or effector function requires a regulated increase and subsequent decrease in the intracellular concentration of Ca 2ϩ ([Ca 2ϩ ] i ). The biochemical events associated with activation of T lymphocytes and leading to Ca 2ϩ entry have been extensively studied (1). Engagement of the TCR leads to the activation of phospholipase C, which subsequently cleaves phosphatidylinositol bisphosphate into inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG). IP 3 , binding to an intracellular receptor, induces the release of Ca 2ϩ from an intracellular storage depot (2). In a receptor-independent manner, the Ca 2ϩ /ATPase inhibitor thapsigargin (3) causes an uncompensated leak of Ca 2ϩ from this internal storage pool. In T lymphocytes, as well as in most electrically nonexcitable cells, this depletion of the intracellular storage pool induces the opening of the plasma membrane Ca 2ϩ entry pathway and permits influx of extracellular Ca 2ϩ (1). Previously, we have provided evidence that the pathway between release of intracellular Ca 2ϩ and influx of extracellular Ca 2ϩ is mediated by Ca 2ϩ -activated calmodulin (4), which permits Ca 2ϩ entry carried by a current we have called I T...

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The Protein Kinase C Family: Heterogeneity and Its Implications

Cited by 719 publications

References 59 publications

Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

Selective Induction of Heparin-binding Epidermal Growth Factor-like Growth Factor by Methylglyoxal and 3-Deoxyglucosone in Rat Aortic Smooth Muscle Cells

A Role for Protein Kinase CβI in the Regulation of Ca2+ Entry in Jurkat T Cells

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