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)

Cyclic nucleotide-independent protein kinase (EC 2.7.1.37) activity was found in the nuclear cap organelle, within which ribosomes of zoospores of Blastocladiella emersonii are sequestered. Two protein kinase activities were resolved from the high-salt wash fraction of zoospore ribosomes by selective adsorption to DEAE-cellulose. Both enzymes phosphorylated in vitro a 32,000 Mr protein of the 40S ribosomal subunit. Phosphorylation of this ribosomal protein, which exhibits electrophoretic properties similar to those of mammalian ribosomal protein S6, was also observed in vivo in 32P-labeled zoospores.
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PMID:Cyclic nucleotide-independent protein kinases from ribosomes and phosphorylation of a single 40S ribosomal subunit protein in zoospores of Blastocladiella emersonii. 685 50

In quiescent cells high levels of protein synthesis are required in order to re-enter the cell cycle upon stimulation. Initiation of polypeptide synthesis is the step most often subject to regulation, controlled in part by phosphorylation of 40 S ribosomal protein S6 and a number of initiation factors. The kinase responsible for S6 phosphorylation is p70S6k. We now show that the p70S6k pathway can be selectively blocked by the aminopurine analogue, SQ 20006. This agent is known to raise cAMP levels, resulting in activation of protein kinase A. We present evidence that the increase in cAMP is not responsible for the inhibitory effect observed. We also show that SQ 20006 can prevent the activation of p70S6k in a rapid and reversible manner. The compound does not exert its inhibitory activity on p70S6k but can inhibit in vitro two protein kinase C isozymes (alpha and gamma). In a B lymphoblastoid cell line, treatment with SQ 20006 results in inhibition of protein synthesis at the initiation stage. In contrast, when tested directly upon the translational machinery in the reticulocyte lysate, inhibition is manifest at both the level of initiation and elongation. The role of protein kinase A in the modulation of p70S6k and the rate of translation is discussed.
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PMID:The phosphodiesterase inhibitor SQ 20006 selectively blocks mitogen activation of p70S6k and transition to S phase of the cell division cycle without affecting the steady state phosphorylation of eIF-4E. 759 97

Many of the effects of growth factors or hormones are mediated through the activation of protein kinase cascades. In this regard, it is well established that the activity of several protein kinases can be dramatically increased when cells are treated with a variety of stimuli. Since 1987, there have been several reports demonstrating that the activity of casein kinase II (CKII) can be acutely increased by hormones or growth factors. However, these are a number of discrepancies regarding the activation of CKII. In this study, we have examined CKII activities in extracts prepared from cells following treatment with stimuli that had been previously shown to elicit dramatic increases in CKII activity. Human WI.38 diploid lung fibroblasts were stimulated with serum or a variety of other stimuli including insulin, platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, or phorbol myristate acetate. Human A431 epidermal carcinoma cells were similarly treated with epidermal growth factor. No reproducible increases in CKII activity were observed in response to any of these treatments. By comparison, a dramatic increase in kinase activity towards a synthetic peptide based on phosphorylation sites within the ribosomal S6 protein was consistently measured. Our observations indicate that CKII is not regulated in a similar manner by growth factors as are the protein kinases of the MAP kinase cascade, e.g., MAP kinase itself or ribosomal protein S6 kinase.
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PMID:Regulation of casein kinase II by growth factors: a reevaluation. 773 11

The role of the p90 ribosomal protein S6 kinase/mitogen-activated protein kinase (RSK/MAPK) signaling pathway in regulating glycogen synthase kinase-3 (GSK-3) activity was investigated. In vitro studies showed that GSK-3 was inactivated by 50% upon incubation with RSK purified from epidermal growth factor (EGF)-stimulated NIH/3T3 cells. Subsequently, the effect of EGF on GSK-3 activity was measured in NIH/3T3 cells that stably overexpressed mutated forms of MAPK kinase (MAPKK). The activation of RSK by EGF was markedly decreased in cell lines expressing the dominant negative MAPKK mutants S222A and K97A and was increased in cells expressing the S222E mutant as compared with control cell lines. EGF induced a rapid decrease in GSK-3 beta activity (50%) in control and S222E cells; however, only 25 and 10% inhibition in GSK-3 beta activity was observed in cell lines expressing the dominant negative mutants K97A and S222A, respectively, suggesting that inhibition of GSK-3 was partially blocked in these cells. Taken together, these results suggest that the action of EGF on GSK-3 inactivation is mediated by the RSK/MAPK signaling pathway in NIH/3T3 cells and provide evidence for a mechanism regulating GSK-3 activity in intact cells.
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PMID:Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. 783 18

The insect prothoracic glands are the source of steroidal molting hormone precursors and the glands are stimulated by a brain neuropeptide, prothoracicotropic hormone (PTTH). Previous work from this laboratory revealed that PTTH acts via a cascade including Ca2+/calmodulin activation of adenylate cyclase, protein kinase A, and the subsequent phosphorylation of a 34 kDa protein (p34) hypothesized, but not proven, to be the S6 protein of the 40S ribosomal subunit. The immunosuppressive macrolide, rapamycin, is a potent inhibitor of cell proliferation, a signal transduction blocker, and also prevents ribosomal S6 phosphorylation in mammalian systems. We demonstrate here that rapamycin inhibited PTTH-stimulated ecdysteroidogenesis in vitro by the prothoracic glands of the tobacco hornworm, Manduca sexta, with half-maximal inhibition at a concentration of about 5 nM. At concentrations above 5 nM, there was a 75% inhibition of ecdysteroid biosynthesis. Similar results were observed with the calcium ionophore (A23187), a known stimulator of ecdysteroidogenesis. Most importantly, the inhibition of ecdysteroid biosynthesis was accompanied by the specific inhibition of the phosphorylation of p34, indicating that p34 indeed is ribosomal protein S6. In vivo assays revealed that injection of rapamycin into day 6 fifth instar larvae resulted in a decreased hemolymph ecdysteroid titer and a dose-dependent delay in molting and metamorphosis. When S6 kinase (S6K) activity was examined using rapamycin-treated prothoracic glands as the enzyme source and a synthetic peptide (S6-21) or a 40S ribosomal subunit fraction from Manduca tissues as substrate, the date revealed that rapamycin inhibited S6K activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:S6 phosphorylation results from prothoracicotropic hormone stimulation of insect prothoracic glands: a role for S6 kinase. 792 36

Mitogen activated protein (MAP) kinases and their target ribosomal protein S6 (RSK) kinases have been recognized as shared components in the intracellular signaling pathways of many diverse cytokines. Recent studies have extended this protein kinase cascade by identifying the major activator of vertebrate MAP kinases as a serine/threonine/tyrosine-protein kinase called MEK, which is related to yeast mating factor-regulated protein kinases encoded by the STE7 and byr1 genes. MEK, in turn, may be activated following its phosphorylation on serine by either of the kinases encoded by proto-oncogenes raf1 or mos, as well as by p78mekk, which is related to the yeast STE11 and byr2 gene products. Isoforms of all of these protein kinases may specifically combine to assemble distinct modules for intracellular signal transmission. However, the fundamental architecture of these protein kinase cascades has been highly conserved during eukaryotic evolution.
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PMID:Networking with mitogen-activated protein kinases. 793 48

Bacteriophage T7 expresses a serine/threonine-specific protein kinase activity during infection of its host, Escherichia coli. The protein kinase (gp0.7 PK), encoded by the T7 early gene 0.7, enhances phage reproduction under sub-optimal growth conditions. It was previously shown that ribosomal protein S1 and translation initiation factors IF1, IF2, and IF3 are phosphorylated in T7-infected cells, and it was suggested that phosphorylation of these proteins may serve to stimulate translation of the phage late mRNAs. Using high-resolution two-dimensional gel electrophoresis and specific immunoprecipitation, we show that elongation factor G and ribosomal protein S6 are phosphorylated following T7 infection. The gel electrophoretic data moreover indicate that elongation factor P is phosphorylated in T7-infected cells. T7 early and late mRNAs are processed by ribonuclease III, whose activity is stimulated through phosphorylation by gp0.7 PK. Specific overexpression and phosphorylation was used to locate the RNase III polypeptide in the standard two-dimensional gel pattern, and to confirm that serine is the phosphate-accepting amino acid. The two-dimensional gels show that the in vivo expression of gp0.7 PK results in the phosphorylation of over 90 proteins, which is a significantly higher number than previous estimates. The protein kinase activities of the T7-related phages T3 and BA14 produce essentially the same pattern of phosphorylated proteins as that of T7. Finally, several experimental variables are analysed which influence the production and pattern of phosphorylated proteins in both uninfected and T7-infected cells.
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PMID:Phosphorylation of elongation factor G and ribosomal protein S6 in bacteriophage T7-infected Escherichia coli. 802 76

A cardiolipin- and protease-activated protein kinase (PAK) has been isolated from cytoplasmic extracts of rat liver. The enzyme (PAK-1) phosphorylates the ribosomal protein S6-(229-239) peptide analogue and can be activated by limited proteolysis. Partial amino acid sequences of tryptic peptides derived from both the purified 116-kDa PAK-1 holoenzyme and its active catalytic fragment reveal that the catalytic domain is most related (50-58% identity) to the protein kinase C family. PAK-1 has protein and peptide substrate specificities distinct from those of known protein kinase C isoforms and is insensitive to inhibition by the protein kinase C-alpha-(19-31) pseudosubstrate peptide. Phosphatidylserine, diacylglycerol, and phorbol ester do not activate PAK-1 toward the S6 peptide substrate. However, other acidic phospholipids, the most effective being cardiolipin, activate PAK-1 to a similar extent as trypsin. The PAK-1 catalytic activities generated through activation by cardiolipin or limited proteolysis were kinetically similar, with Km values of 3.6 and 3.4 microM, respectively, for the S6-(229-239) peptide substrate. However, differences were observed in the catalytic activities with protamine sulfate and the glycogen synthase-(1-12) peptide analogue as substrates. It was concluded that PAK-1 is a phospholipid-regulated protein kinase with a primary structure, substrate specificity, and mechanism of regulation in vitro distinct from those of any known member of the protein kinase C superfamily.
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PMID:A cardiolipin-activated protein kinase from rat liver structurally distinct from the protein kinases C. 805 Oct 89

The predominant 40 S ribosomal protein S6 kinase in skeletal muscle extracts from insulin-treated rats was purified over 10,000-fold to near homogeneity with approximately 4.5% recovery of starting activity. This S6 kinase was resolved from the catalytic subunit of cAMP-dependent protein kinase only by the seventh and final column chromatography step. The purified S6 kinase migrated as a tight doublet of approximately 31 kDa on an SDS-polyacrylamide gel, and it was eluted from gel filtration columns with a similar apparent M(r), which indicated that the enzyme exists as a monomer. This S6 kinase was immunologically distinct from the other known insulin-activated S6 kinases, i.e. p70S6K and p90rsk. It was inhibited by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid and beta-glycerophosphate at concentrations routinely used to stabilize p70S6K and p90rsk. In addition to S6, phosvitin was also a substrate, whereas myelin basic protein, casein, protamine, and histones were poorly phosphorylated if at all by the purified S6 kinase. The purified enzyme was inactivated upon incubation with serine/threonine-specific protein phosphatase 2A, which indicated that it may be an intermediary component in a cascade of insulin-activated protein kinases.
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PMID:Purification and characterization of a novel ribosomal S6 kinase from skeletal muscle of insulin-treated rats. 812 8

The substrate specificity of mitogen-activated protein (MAP) kinase-activated protein kinase-2 (MAPKAP kinase-2) was investigated by using synthetic peptides related to the N-terminus of glycogen synthase. The minimum sequence required for efficient phosphorylation was found to be Xaa-Xaa-Hyd-Xaa-Arg-Xaa-Xaa-Ser-Xaa-Xaa, where Hyd is a bulky hydrophobic residue (Phe > Leu > Val >> Ala), and the peptide Lys-Lys-Phe-Asn-Arg-Thr-Leu-Ser-Val-Ala was phosphorylated with a Km of 9.3 microM and Vmax. of 10 mumol/min per mg. MAPKAP kinase-1 (a homologue of ribosomal protein S6 kinase) also requires an arginine three residues N-terminal to the serine (position n-3), but not a hydrophobic residue at position n-5. Neither MAPKAP kinase-1 nor MAPKAP kinase-2 could tolerate a proline residue at position n + 1, indicating that their specificities do not overlap with that of MAP kinase. The specificity of calmodulin-dependent protein kinase-II resembled that of MAPKAP kinase-2, except that it could tolerate replacement of the arginine by a lysine and the phosphorylation-site serine by a threonine residue. Partial cDNAs encoding MAPKAP kinase-2 were isolated from rabbit and human skeletal muscle and human teratocarcinoma libraries, and Northern-blotting experiments revealed a single 3.3 kb mRNA transcript present at similar levels in six human tissues examined. The catalytic domain was most similar (35-40% identity) to calmodulin-dependent protein kinases II and IV, phosphorylase kinase, putative serine kinase H1 and the C-terminal domain of MAPKAP kinase-1, which form one branch of the protein kinase phylogenetic tree. The sequence N-terminal to the catalytic domain is proline-rich and contains two putative SH3-binding sites. The threonine residue phosphorylated by MAP kinase lies immediately C-terminal to the catalytic domain and is followed by a nuclear localization signal, Lys-Lys-(Xaa)10-Lys-Arg-Arg-Lys-Lys, near the C-terminus.
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PMID:The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2. 828 84


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