Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the eukaryotic elongation factor (eEF-2) specific, Ca2+ and calmodulin dependent protein kinase III (CaM PK III) was studied in homogenated Ehrlich ascites tumour cells. The eEF-2 kinase activity was determined in the presence of an excess of the substrate, i.e., non-limiting concentrations of eEF-2. The homogenates showed both kinase and phosphatase activity. The latter activity was inhibited by the protein phosphatase 2A inhibitor okadaic acid. Analysis of the kinase using cells from defined stages of the cell cycle showed that the highest activity was found in cells from the early S-phase, whereas the phosphatase activity was most pronounced during the G2+M phase.
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PMID:Increased activity of the eEF-2 specific, Ca2+ and calmodulin dependent protein kinase III during the S-phase in Ehrlich ascites cells. 165 15

Treatment of PC12 cells with nerve growth factor (NGF), epidermal growth factor (EGF), or agents that raise intracellular cyclic AMP (cAMP) levels (e.g., forskolin) reduces the activity of calmodulin-dependent protein kinase III (CaM-PK III) over a period of 8 h. The mechanism of this effect of NGF has now been examined in more detail, making use of a mutant PC12 cell line (A126-1B2) that is deficient in cAMP-dependent protein kinase activity. Control experiments showed that A126-1B2 cells retain other NGF-mediated responses (e.g., the induction of ornithine decarboxylase, a cAMP-independent event) and contain a complement of CaM-PK III and its substrate, elongation factor-2, comparable to that of wild-type cells. The ability of NGF or forskolin, but not of EGF, to down-regulate CaM-PK III was markedly attenuated in A126-1B2 compared to wild-type cells. Treatment of wild-type cells with the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, enhanced the effects of NGF, but not of EGF. The possibility that NGF led to a stimulation of cAMP-dependent protein kinase activity in wild-type cells was assessed by measurement of the "activation ratio" (-cAMP/+cAMP) of this enzyme before and at various times after NGF addition. A small, but significant, increase in the activation ratio from 0.3 to 0.48 was observed, reaching a peak 5 min after NGF treatment. EGF had no effect on the activation ratio in wild-type cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nerve growth factor-induced down-regulation of calmodulin-dependent protein kinase III in PC12 cells involves cyclic AMP-dependent protein kinase. 168 74

The activity of the eukaryotic elongation factor 2 (eEF-2)-specific Ca(2+)- and calmodulin-dependent protein kinase III (CaM PK III) is regulated by phosphorylation. The kinase can be inactivated by treatment with alkaline phosphatase and subsequently reactivated by endogenous protein kinase. This kinase can be substituted for by the catalytic subunit of cAMP-dependent protein kinase but not by casein kinase II. The purified kinase preparation contains only one protein as judged by gel electrophoresis. This protein has a molecular mass of approximately 90 kDa and an isoelectric point of 5.2. Reactivation of the eEF-2 kinase is associated with the phosphorylation of this protein. The amino acid sequence obtained from the 90-kDa protein reveals substantial homology with that of murine heat shock protein 86 (HSP 86) a member of the HSP 90-family. Conventional preparations of HSP 90 contain an inactive eEF-2 kinase that could be activated after dephosphorylation and phosphorylation by the catalytic subunit of cAMP-dependent protein kinase.
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PMID:Phosphorylation regulates the activity of the eEF-2-specific Ca(2+)- and calmodulin-dependent protein kinase III. 188 75

A major substrate, Mr 100,00 (100 kDa), for a Ca2+/calmodulin (CaM)-dependent protein kinase found in many mammalian tissues has been purified from rat pancreas. The purified substrate was used to identify and partially purify a CaM-dependent protein kinase (CaM kinase III) from rat pancreas. The physical properties and substrate specificity of CaM kinase III were distinct from those of all known CaM-dependent protein kinases. Only CaM kinase III was able to phosphorylate the 100-kDa protein; synapsin I, phosphorylase b, myosin light chain, and histone were poor substrates for this enzyme. Polyclonal antibodies, raised against the purified 100-kDa protein, recognized the protein in a variety of mammalian tissues and cell lines. Immunoassay revealed that the 100-kDa protein made up 0.3-1.7% of the total cytosolic protein in these samples. Analysis of CaM kinase III revealed that the enzyme had a similar widespread tissue distribution. These results demonstrate the existence of a fifth CaM-dependent protein phosphorylation system present in high levels in animal cells.
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PMID:Identification of calmodulin-dependent protein kinase III and its major Mr 100,000 substrate in mammalian tissues. 390 54

The mitogenic activity of several growth factors is mediated by calcium-dependent signal transduction. Calmodulin (CaM) binding proteins such as CaM-dependent protein kinases are important components of this pathway and may be altered in diseases characterized by abnormal cell growth. CaM kinase II is believed to regulate the phosphorylation of microtubular-associated proteins and control the initiation of DNA synthesis. Furthermore, drugs that inhibit CaM-mediated signal transduction also inhibit cellular proliferation and are cytotoxic to numerous malignant cell lines, including those established from malignant gliomas. Yet, little is known about CaM-dependent protein kinases in these tumors. Therefore, we have investigated the activity and distribution of CaM-dependent protein kinase II in normal and malignant glial tissues, a kinase believed to play a critical role in cell cycle regulation. C6 and 9L cells contained kinase activities that were activated by Ca2+/CaM and inhibited by trifluoperazine. Tissue extracts from these cell lines and from rat brain white matter phosphorylated exogenous synapsin I in a pattern consistent with the presence of CaM kinase II activity as determined by phosphopeptide mapping. CaM kinase II activity was confirmed using a specific peptide substrate and inhibitor. An unexpected finding was that glioma lines, but not rat brain white matter, also contained a CaM-dependent protein kinase detected by the phosphorylation of a M(r) 100,000 protein, subsequently identified as elongation factor 2, the only known substrate for CaM kinase III.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calmodulin-dependent protein kinases in rat glioblastoma. 764 41

We have previously shown that Ca2+/calmodulin-dependent phosphorylation of the 100-kDa protein dramatically increases during the early period of myoblast fusion and treatment of calmodulin antagonists, such as trifluoperazine, blocks the fusion. Here, we show that cAMP treatment of primary cultures of chick embryonic myoblasts blocks 100-kDa protein phosphorylation. This effect is dose-dependent and can be reversed upon removal of the nucleotide from the culture media. However, cAMP shows little or no effect on accumulation of the 100-kDa protein. Furthermore, phosphorylation of the 100-kDa protein by the partially purified Ca2+/calmodulin-dependent protein kinase (CaM kinase III) from cAMP-treated cells occurs to a much lower extent than that from untreated cells. Nevertheless, cAMP-sensitive protein kinase does not seem to be directly involved in phosphorylation and inactivation of CaM kinase III, because preincubation of cAMP with the myoblast extracts lacking the endogenous 100-kDa protein does not show any effect on activity of CaM kinase III. Similar to its effect on 100-kDa protein phosphorylation, cAMP reversibly inhibits the fusion of cultured myoblasts. Moreover, treatment with forskolin or theophylline, which is known to elevate the intracellular cAMP level, also reversibly blocks both protein phosphorylation and myoblast fusion. On the other hand, cAMP shows little or no effect on accumulation of muscle-specific proteins, such as creatine kinase and tropomyosin. These results suggest that cAMP is involved in down-regulation of both 100-kDa protein phosphorylation and membrane fusion of cultured myoblasts. These results also suggest that the cAMP-mediated inhibition of 100-kDa protein phosphorylation may be associated with its inhibitory effect on myoblast fusion.
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PMID:Cyclic AMP negatively modulates both Ca2+/calmodulin-dependent phosphorylation of the 100-kDa protein and membrane fusion of chick embryonic myoblasts. 808 35

Specificities of several known protein kinase inhibitors were evaluated using an assay system in which activities of protein kinase A, protein kinase C, protein tyrosine kinase and calmodulin-dependent protein kinase III were simultaneously detected. Inhibitory spectra of H-89, K252a, H-7, staurosporine, tyrphostin and herbimycin A observed in the assay system were similar to those reported in the purified protein kinase assay systems. It was also found that KN-62 selectively inhibited calmodulin-dependent protein kinase III activity. These data suggest that the assay system may be effective and practicable in evaluating specificities and screening of new protein kinase inhibitors.
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PMID:Evaluation of protein kinase inhibitors in an assay system containing multiple protein kinase activities. 829 1

The catalytic subunit of cyclic AMP-dependent protein kinase (PKA) phosphorylated purified calcium/calmodulin-dependent eukaryotic elongation factor-2 (eEF-2) kinase, isolated from rabbit reticulocyte lysates. It maximally incorporated about 1 mol of phosphate/mol of eEF-2 kinase. The Km of eEF-2 kinase for PKA was calculated to be 7 microM. Phosphorylation of eEF-2 kinase by PKA induced calcium-independent activity which amounted to 40-50% of the total activity measured in the presence of calcium. Furthermore, the level of calcium-independent activity induced by phosphorylation by PKA was similar to that induced by the calcium-stimulated autophosphorylation of eEF-2 kinase. Phosphopeptide mapping of eEF-2 kinase labelled by autophosphorylation and by PKA revealed a number of common phosphopeptides. This suggests that PKA may phosphorylate the same site(s) which are phosphorylated autocatalytically and which are responsible for the induction of calcium-independent activity. The possible implications these findings have for the control of translation are discussed.
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PMID:Cyclic AMP-dependent protein kinase phosphorylates rabbit reticulocyte elongation factor-2 kinase and induces calcium-independent activity. 832 70

We report a simple method that permits simultaneous detection of multiple protein kinase activities using postnuclear supernatant of v-src transformed NIH3T3 cells. A supernatant is incubated with activators of protein kinases and [gamma-32P]ATP, and the phosphorylated proteins are analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The method enables detection of activities of at least four protein kinases (protein kinase A, protein kinase C, protein tyrosine kinase(s), and calmodulin-dependent protein kinase III) on a single gel. Experiments using various specific activators and inhibitors of protein kinases indicated that this method can, in crude preparations, reliably detect the protein kinase activities intended for measurement. Protein kinase C activity disappeared when membranes were solubilized, demonstrating the importance of membrane environment for its function. This method should be particularly useful for evaluating and screening protein kinase inhibitors.
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PMID:Method for simultaneous detection of protein kinase A, protein kinase C, protein tyrosine kinase, and calmodulin-dependent protein kinase activities. 836 81

Elongation factors involved in polypeptide chain elongation are considered to be rate limiting for the slowing down of total protein synthesis during ageing. The activities of elongation factors are themselves regulated by various means, including phosphorylation. Here we have compared the activity of a protein kinase, called calcium- and calmodulin-dependent protein kinase III (CaM PK III), specific for the phosphorylation of elongation factor eEF-2, in cell-free extracts prepared from livers isolated from young and old male Fischer 344 rats maintained under freely fed or calorie-restricted dietary regimes. There was a significant increase of more than 70% in the activity of CaM PK III in 24 month old freely fed rat livers as compared with young animals. This age-related increase was found but to a lower extent (46%) in calorie-restricted rats of the same age. Therefore, slowing down of ageing in calorie-restricted animals is also reflected at the level of the regulation of the activity of protein elongation factor eEF-2 by CaM PK III.
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PMID:Elongation factor 2-specific calcium and calmodulin dependent protein kinase III activity in rat livers varies with age and calorie restriction. 838 44


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