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)

Stress response requires the precise modulation of gene expression in response to changes in growth conditions. This report demonstrates that selective nuclear mRNA degradation is required for both the cell wall stress response and the regulation of the cell wall integrity checkpoint. More specifically, the deletion of the yeast nuclear dsRNA-specific ribonuclease III (Rnt1p) increased the expression of the mRNAs associated with both the morphogenesis checkpoint and the cell wall integrity pathway, leading to an attenuation of the stress response. The over-expression of selected Rnt1p substrates, including the stress associated morphogenesis protein kinase Hsl1p, in wild-type cells mimicked the effect of RNT1 deletion on cell wall integrity, and their mRNAs were directly cleaved by the recombinant enzyme in vitro. The data supports a model for gene regulation in which nuclear mRNA degradation optimizes the cell response to stress and links it to the cell cycle.
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PMID:RNA-dependent regulation of the cell wall stress response. 2257 66

Bacteriophage T7 encodes a serine/threonine-specific protein kinase that phosphorylates multiple cellular proteins during infection of Escherichia coli. Recombinant T7 protein kinase (T7PK), normally purified in phosphorylated form, exhibits a modest level of phosphotransferase activity. A procedure is described that provides dephosphorylated T7PK with an enhanced ability to phosphorylate protein substrates, including translation initiation factor IF1 and the nuclease domain of ribonuclease III. Mass spectrometric analysis identified Thr12 as the site of IF1 phosphorylation in vitro. T7PK undergoes Mg(2+)-dependent autophosphorylation on Ser216 in vitro, which also is modified in vivo. The inability to isolate the presumptive autophosphorylation-resistant T7PK Ser216Ala mutant indicates a toxicity of the phosphotransferase activity and suggests a role for Ser216 modification in limiting T7PK activity during infection.
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PMID:Bacteriophage T7 protein kinase: Site of inhibitory autophosphorylation, and use of dephosphorylated enzyme for efficient modification of protein in vitro. 2295 Nov 89

Ribonuclease III (RNase III) is a conserved, gene-regulatory bacterial endonuclease that cleaves double-helical structures in diverse coding and noncoding RNAs. RNase III is subject to multiple levels of control, reflective of its global regulatory functions. Escherichia coli (Ec) RNase III catalytic activity is known to increase during bacteriophage T7 infection, reflecting the expression of the phage-encoded protein kinase, T7PK. However, the mechanism of catalytic enhancement is unknown. This study shows that Ec-RNase III is phosphorylated on serine in vitro by purified T7PK, and identifies the targets as Ser33 and Ser34 in the N-terminal catalytic domain. Kinetic experiments reveal a 5-fold increase in kcat and a 1.4-fold decrease in Km following phosphorylation, providing a 7.4-fold increase in catalytic efficiency. Phosphorylation does not change the rate of substrate cleavage under single-turnover conditions, indicating that phosphorylation enhances product release, which also is the rate-limiting step in the steady-state. Molecular dynamics simulations provide a mechanism for facilitated product release, in which the Ser33 phosphomonoester forms a salt bridge with the Arg95 guanidinium group, thereby weakening RNase III engagement of product. The simulations also show why glutamic acid substitution at either serine does not confer enhancement, thus underscoring the specific requirement for a phosphomonoester.
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PMID:Mechanism of Ribonuclease III Catalytic Regulation by Serine Phosphorylation. 2715 Jun 69

As a type III ribonuclease (RNase III) specifically cleaving double-stranded RNA substrates into short fragments, Dicer is indispensable in a range of physi/pathologic processes, e.g., nutrient deprivation, hypoxia, or DNA damage. Therefore, much interest has been paid to the research of this protein as well as its products like microRNAs (miRNAs). The close relationship between Dicer levels and fluctuations of nutrient availability suggests that the protein participates in the regulation of systemic energy homeostasis. Through miRNAs, Dicer regulates the hypothalamic melanocortin-4 system and central autophagy promoting energy expenditure. Moreover, by influencing canonical energy sensors like adenosine monophosphate-activated protein kinase (AMPK) or mammalian target of rapamycin (mTOR), Dicer favors catabolism in the periphery. Taken together, Dicer might be targeted in the control of energy dysregulation. However, factors affecting its RNase activity should be noted. Firstly, modulation of structural integrity affects its role as a ribonuclease. Secondly, although previously known as a cytosolic endoribonuclease, evidence suggests Dicer can relocalize into the nucleus where it could also produce small RNAs. In this review, we probe into involvement of Dicer in energy homeostasis as well as its structural integrity or cellular distribution which affects its ability to produce miRNAs, in the hope of providing novel insights into its mechanism of action for future application.
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PMID:Function of Dicer with regard to Energy Homeostasis Regulation, Structural Modification, and Cellular Distribution. 3277 63


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