The protein kinase C family

Azzi, Angelo; Boscoboinik, Daniel; Hensey, Carmel

doi:10.1007/978-3-642-78046-2_15

Cited by 36 publications

(51 citation statements)

References 155 publications

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“…PKC consists of at least eight isozymes, several of which are coexpressed" in single cells and unequally distributed between cytosol and membranes [1,37,48]. In general, activation of PKC is associated with increased membrane binding of the enzyme and a parallel decrease in cytosolic activity.…”

Section: Introductionmentioning

confidence: 99%

“…In general, activation of PKC is associated with increased membrane binding of the enzyme and a parallel decrease in cytosolic activity. Prolonged membrane association may initiate proteolytic degradation or "down-regulation", a process which affects different PKC isozymes to a different extent and at different rates [1,37,48]. It was therefore taken as evidence for a possible role of PKC as mediator of hypoxic signal transduction, when a translocation of PKC from cytosol to membranes and a reduction of its activity was observed in fetal rat brain during anoxia [34], and in renal LLCPK1 cells upon hypoxic incubation in vitro [42].…”

Section: Introductionmentioning

confidence: 99%

“…It was therefore taken as evidence for a possible role of PKC as mediator of hypoxic signal transduction, when a translocation of PKC from cytosol to membranes and a reduction of its activity was observed in fetal rat brain during anoxia [34], and in renal LLCPK1 cells upon hypoxic incubation in vitro [42]. Moreover, hypoxia-mediated impaired differentiation of LLCPK1 cells [41] was mimicked upon treatment of normoxic cells with phorbol esters [42], known activators of PKC [1,37,48]. In pulmonary artery smooth muscle cells, hypoxia is known to induce contraction and proliferation.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, one group found that the reduction of EPO formation upon treatment with phorbol esters in Hep G2 cells is due to depletion of PKC [31], whereas others did not obtain clear evidence that down-regulation of PKC is associated with the inhibition of EPO formation [33]. Finally, synthetic analogues of diacylglycerol, the endogenous activator of PKC [1,37,48] were found to inhibit EPO secretion in renal carcinoma cells [25] and Hep 3B cells [19], but had no effect on EPO production in Hep G2 cells [33]. It is possible that these different results may be due to intrinsic properties of the different tumour cell lines under investigation, and overall it remains unclear whether activation of PKC inhibits EPO formation, or if conversely, down-regulation and inhibition of PKC reduces EPO production under certain conditions.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

et al. 1994

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Abstract.To define the role of protein kinase C (PKC) in oxygen-dependent production of erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated at different oxygen tensions in the absence and presence of phorbol esters, vasopressin, and structurally different kinase inhibitors. Upon reduction of oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with phorbol 12-myristate-13 acetate (PMA) attenuated hypoxiainduced EPO mRNA levels dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA disappeared upon treatment for more than 5 h and was completely lost after incubation for 9 and 18 h in the presence of 10 -6 M and 10 -7 M PMA, respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta, epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO expression was associated with depletion of any of these isozymes. Conversely, PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation of PKC alpha from cytosol to membranes and the time-and dose-dependent attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation, independent of effects on total RNA synthesis, as determined by [3H]uridine incorporation, was also found in the presence of the kinase inhibitor staurosporine (EDso --2 • 10 s M) and three structurally related derivatives with increased selectivity for PKC (RO 317549, EDso --1 • -6 M; RO 318220, EDso --lX

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

et al. 1994

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“…The PKC proteins are a family of serine-threonine kinases that are involved in a range of cellular processes, including growth and differentiation (Azzi et al, 1992;Gescher, 1992). The precise mechanism by which activation of PKC can elicit such a variety of biological responses is unknown.…”

mentioning

confidence: 99%

Bryostatin 1-tamoxifen combinations show synergistic effects on the inhibition of growth of P388 cells in vitro

McGown

Jayson²,

Pettit³

et al. 1998

Br J Cancer

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Summary This study shows that combinations of bryostatin 1, a novel modulator of protein kinase C currently under clinical evaluation, with the anti-oestrogenic agent tamoxifen caused a large synergistic enhancement of growth inhibition in P388 cells in vitro. The growth-inhibitory effects of bryostatin 1 in the presence of non-inhibitory concentrations of tamoxifen were increased by approximately 200-fold, whereas growth inhibition by tamoxifen in the presence of non-inhibitory concentrations of bryostatin 1 were increased over 30-fold. These data have been confirmed by isobologram analysis. The precise mechanism underlying this effect is unknown, although preliminary data implicating protein kinase C is presented. The magnitude of this synergistic effect, together with evidence of clinical responses seen when these agents were given sequentially in ovarian cancer, merits further study.

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Protein kinase C involvement in the resting and interferon-?-induced K+ channel profile of microglial cells

Visentin

Levi

1997

J. Neurosci. Res.

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The protein kinase C family

Cited by 36 publications

References 155 publications

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

Bryostatin 1-tamoxifen combinations show synergistic effects on the inhibition of growth of P388 cells in vitro

Protein kinase C involvement in the resting and interferon-?-induced K+ channel profile of microglial cells

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