Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both phospholipid/calcium (PL/Ca2+) activated and calmodulin/Ca2+ (CaM/Ca2+)activated protein kinase systems were found in rat pancreatic extracts treated with Sephadex G-25. At least four substrate proteins for PL/Ca2+-activated kinase and one for a CaM/Ca2+-activated kinase were noted. Polymyxin B, an amphipathic antibiotic, was over 100-fold more potent as an inhibitor of PL/Ca2+-dependent protein phosphorylation than of the CaM/Ca2+-dependent system (Ki = app. 7 microM v. 950 microM). Fluphenazine inhibited both PL/Ca2+- and CaM/Ca2+-dependent protein kinases with equal potency, as did dibucaine. Inhibition by polymyxin B of PL/Ca2+-dependent phosphorylation could be overcome by increased amounts of phosphatidylserine. Low concentrations (10(-5)M) of polymyxin B completely inhibited carbachol-stimulated amylase release from intact pancreatic acini. These results indicate that polymyxin B may be useful in delineating the relative roles of PL/Ca2+-dependent and CaM/Ca2+-dependent protein phosphorylation in biological systems and suggest a potential role for the PL/Ca2+-activated kinase in regulation of pancreatic exocrine function.
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PMID:Dual calcium-dependent protein phosphorylation systems in pancreas and their differential regulation by polymyxin B1. 620 37

The addition of the tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate resulted in activation of calcium-sensitive phospholipid-dependent protein kinase which was dependent on the presence of phospholipid but was essentially independent of calcium. Fluphenazine, which is an effective inhibitor of the ability of this phorbol ester to stimulate proliferation in calcium-deprived non-neoplastic cells, inhibited the enzyme in the absence or presence of the phorbol ester (Ki = 16 microM). Fluphenazine inhibition was competitive with phospholipid but non-competitive with 12-O-tetradecanoyl phorbol-13-acetate.
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PMID:Effect of fluphenazine on the stimulation of calcium-sensitive phospholipid-dependent protein kinase by 12-O-tetradecanoyl phorbol-13-acetate. 664

The sequence of molecular events linking depolarisation-dependent calcium influx to calcium-stimulated protein phosphorylation is unknown. In this study the effect of the neuroleptic drug fluphenazine on depolarisation-dependent protein phosphorylation was investigated using an intact postmitochondrial pellet isolated from rat cerebral cortex. Fluphenazine, in a dose-dependent manner, completely inhibited the increases in protein phosphorylation observed previously. The concentration of fluphenazine required for 50% inhibition varied for different phosphoproteins but for synapsin I was 123 microM. Other neuroleptics produced effects similar to fluphenazine with their order of potency being thioridazine greater than haloperidol greater than trifluoperazine greater than fluphenazine greater than chlorpromazine. Fluphenazine also increased the phosphorylation of proteins in nondepolarised controls at concentrations of 20 and 60 microM. The inhibition of depolarisation-dependent phosphorylation was apparently not due to a loss of synaptosomal integrity or viability, a decrease in calcium uptake, a change in substrate availability, or to a change in protein phosphatase activity. The data are most consistent with an inhibition of protein kinase activity by blockade of calmodulin or phospholipid activation.
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PMID:Depolarisation-dependent protein phosphorylation in rat cortical synaptosomes is inhibited by fluphenazine at a step after calcium entry. 674 28