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)

During differentiation of human promyelocytic HL60 cells into monocytes there are sustained increases in intracellular pH and Na+/H+ antiporter activity. Here we show that increased transcription and expression of the gene for the Na+/H+ antiporter precedes phorbol 12-myristate 13-acetate (PMA)-induced HL60 cell differentiation. PMA increased steady-state Na+/H+ antiporter mRNA levels approximately 50-fold within 8 h (at which time less than 15% of cells had differentiated). This increase was due to an increased transcriptional rate as determined by nuclear run on. Immunoprecipitation of [35S]methionine-labeled Na+/H+ antiporter using an antiporter fusion protein antibody (RP1-c28) showed an equivalent increase in Na+/H+ antiporter protein synthesis. The synthetic diacylglycerol, 1-oleolyl-2-acetylglycerol, an activator of protein kinase C, which unlike PMA did not cause differentiation, failed to induce Na+/H+ antiporter mRNA. Furthermore, inhibition of PMA-induced differentiation by either sphingosine or cycloheximide prevented accumulation of Na+/H+ antiporter mRNA. Together, these findings strongly suggest a close association of Na+/H+ antiporter induction with HL60 cell differentiation. The HL60 cell system is a promising model to study the mechanisms of Na+/H+ antiporter gene regulation and its function in differentiation.
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PMID:Na+/H+ antiporter gene expression during monocytic differentiation of HL60 cells. 164 22

The growth factor-activated Na+/H+ exchanger is regulated by numerous stimuli, including polypeptide hormones, phorbol esters, cell acidity, and cell shrinkage. To determine whether this regulation occurs at a common site on the cytoplasmic domain of the Na+/H+ exchanger, we microinjected polyclonal antibodies (RP1-c28) to the C-terminal 157 amino acids of the molecule and measured cell pH changes after application of a variety of stimuli known to activate the Na+/H+ exchanger. Microinjection of approximately 10 fg of RP1-c28 antibody, but not control IgG, into single cultured fibroblasts blocked subsequent activation of the exchanger by both endothelin and alpha-thrombin. In contrast, microinjected RP1-c28 did not prevent activation of Na+/H+ exchange by phorbol esters, consistent with the observation that both endothelin-1 and alpha-thrombin retained the ability to activate exchange activity in protein kinase C-depleted cells. Finally, activation of Na+/H+ exchange by both cell acidity and osmotic shrinkage was also unaffected by microinjected RP1-c28 antibody. These data indicate that activation of Na+/H+ exchange by endothelin-1 and alpha-thrombin is mechanistically distinct both from activation by protein kinase C and activation by physical factors and probably occurs at a separate site on the exchanger molecule.
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PMID:Role of cytoplasmic domain of the Na+/H+ exchanger in hormonal activation. 838 29

Effects of procaine on a central neuron (RP1) of the giant African snail (Achatina fulica Ferussac) were studied pharmacologically. The RP1 neuron showed spontaneous firing of action potential. Extra-cellular application of procaine (10 mM) reversibly elicited bursts of potential. The bursts of potential elicited by procaine were not blocked after administration of (1) prazosin, propranolol, atropine, d-tubocurarine, (2) calcium-free solution, (3) ryanodine (4) pretreatment with KT-5720 or chelerythrine. The bursts of potential elicited by procaine were blocked by adding U73122 (10 microM) and the bursts of potential were decreased if physiological sodium ion was replaced with lithium ion or incubated with either neomycin (3.5 mM) or high magnesium solution (30 mM). Preatment with U73122 (10 microM) blocked the initiation of bursts of potential. Ruthenium red (100 microM) or caffeine (10 mM) facilitated the procaine-elicited bursts of potential. It is concluded that procaine reversibly elicits bursts of potential in the central snail neuron. This effect was not directly related to (1) the extra-cellular calcium ion fluxes, (2) the ryanodine sensitive calcium channels in the neuron, or (3) the PKC or PKA related messenger systems. The procaine-elicited bursts of potential were associated with the phospholipase activity and the calcium mobilization in the neuron.
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PMID:Effects of procaine on a central neuron of the snail, Achatina fulica Ferussac. 1568 Jan 72