Global ETD Search

1	Autophosphorylation and Autoactivation of an S6/H4 Kinase Isolated From Human Placenta Dennis, Patrick B. (Patrick Brian) 05 1900 (has links) A number of protein kinases have been shown to undergo autophosphorylation, but few have demonstrated a coordinate increase or decrease in enzymatic activity as a result. Described here is a novel S6 kinase isolated from human placenta which autoactivates through autophosphorylation in vitro. This S6/H4 kinase, purified in an inactive state, was shown to be a protein of Mr of 60,000 as estimated by SDS-PAGE and could catalyze the phosphorylation of the synthetic peptide S6-21, the histone H4, and myelin basic protein. Mild digestion of the inactive S6/H4 kinase with trypsin was necessary, but not sufficient, to activate the kinase fully Placenta. Protein kinases. Phosphorylation. autophosphorylation kinase
2	Autoregulatory and structural control of CaMKII substrate specificity Johnson, Derrick Ethan 06 July 2016 (has links) Indiana University-Purdue University Indianapolis (IUPUI) / Calcium/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a multimeric holoenzyme composed of 8–14 subunits from four closely related isoforms (α, β, γ, δ). CaMKII plays a strategic, multifunctional role in coupling the universal second messenger calcium with diverse cellular processes including metabolism, cell cycle control, and synaptic plasticity. CaMKII exhibits broad substrate specificity, targeting numerous substrates with diverse phosphorylation motifs. Binding of the calcium sensor CaM to the autoregulatory domain (ARD) of CaMKII functions to couple kinase activation with calcium signaling. Important sites of autophosphorylation, namely T287 and T306/7 (δ isoform numbering), reside within the ARD and control either CaM dependence or ability to bind to CaMKII respectively, thus determining various activation states of the kinase. Because autophosphorylation is critical to the function of CaMKII in vivo, we sought to determine the relationship between the activation state of the kinase and substrate selectivity. We show that the ARD of activated CaMKII tunes substrate selectivity by competing for substrate binding to the catalytic domain, thus functioning as a selectivity filter. Specifically, in the absence of T287 autophosphorylation, substrate phosphorylation is limited to high-affinity, consensus substrates. T287 autophosphorylation restores maximal kinase activation and broad substrate selectivity by disengaging ARD filtering. The unique multimeric architecture of CaMKII is an ideal sensor which encodes calcium-spike frequency into graded levels of subunit activation/autophosphorylation within the holoenzyme. We find that differential activation states of the holoenzyme produce distinct substrate phosphorylation profiles. Maximal holoenzyme activation/autophosphorylation leads to further broadening of substrate specificity beyond the effect of autophosphorylation alone, which is consistent with multivalent avidity. Thus, the ability of calcium-spike frequency to regulate T287 autophosphorylation and holoenzyme activation permits cellular activity to dictate switch-like behavior in substrate selectivity that is required for diverse cellular responses by CaMKII. Autophosphorylation Autoregulation CaMKII Phosphorylation Substrate selectivity
3	Structure-Function Analysis of GSK-3 Isoforms Buescher, Jessica L. 03 September 2010 (has links) No description available. Biochemistry GSK-3 tau Wnt autophosphorylation structure-function
4	The localisation and regulation of phosphatidylinositol-4-phosphate 5-Kinase gamma splice variants and the discovery of a new mammalian splice variant, PIP5KIγ_v6 Xia, Yang January 2011 (has links) Type I PIP kinases (phosphatidylinositol 4-phosphate 5-kinases, PIP5Ks) catalyse the majority of cellular synthesis of PI(4,5)P2. To date, three mammalian isoforms (r1, r2, r3) have been found. PIP5KIr is subject to complex C-terminal splice variation, enhancing its transcriptional diversity through evolution and producing at least 5 known spliceoforms in the mammals. This study addresses several important questions. (1) Several remarkable differences have been discovered between the neuronal splice variant PIP5KIr_i3 and its close variant, Ir_i2, whose peptide lacks a 26-AA insert near its C-terminus. This study attempts to map these behavioural differences onto motifs within the peptide insert. Furthermore, a site of point mutation is identified near the activation loop, which amplifies the above differences. (2) This study documents properties of the more recently discovered PIP5KIr_i3, about which relatively little is known, for example, the regulation of its subcellular localisation, kinase activity and post-translational modifications. By site-directed mutagenesis and examining more closely several crucial motifs, insight is gained into the putative relationship between the enzyme’s phosphorylation state, cellular localisation, lipid kinase activity and autophosphorylation. (3) The discovery of a new PIP5KIr splice variant, Ir_v6, is described. First discovered in rodents, PIP5KIr_i6 encompasses the 26-AA insert of Ir_i3, but lacks the common C-terminus of Ir_i2 and Ir_i3 which contains peptide motifs that have several roles in vivo. A polyclonal antibody against the C-terminus of Ir_i6 was also developed. Preliminary characterisation of Ir_i6 demonstrates a similar subcellular localisation, but a wider expression profile than its close relative, Ir_i3, suggesting potentially differential functions across tissues and at various developmental stages. (4) The existence of Ir_v3 and Ir_v6 is also confirmed in humans. In light of recent findings of other novel human spliceoforms, this is shown to be a case of intra-exonic splicing producing “alternative 5’ splice site” exons in the human. Overall, this thesis should help to better understand the regulation and physiological roles of PIP5KIr and, specifically, its different splice variants. 615.1
5	Pathogenicity of a minimal organism: Role of protein phosphorylation in Mycoplasma pneumoniae / Pathogenität eines Minimalorganismus: Die Rolle von Proteinphosphorylierungen in Mycoplasma pneumoniae Schmidl, Sebastian 02 November 2010 (has links) No description available. 570 Biowissenschaften, Biologie Biology (incl. Psychology) Proteinphosphorylierung Autophosphorylierung Phosphozucker-Mutase Glycolyse Glycerol-Metabolismus Phospholipid-Metabolismus Pathogenität Minimalorganismus protein phosphorylation autophosphorylation phosphosugar mutase glycolysis glycerol metabolism phospholipid metabolism pathogenesis minimal organism 42.13 42.30
6	DISTINCT ROLES OF THE aD HELIX IN aCAMKII ACTIVATION CHARACTERIZED USING A DE NOVO MUTATION FROM CHILDREN WITH LEARNING DISABILITIES Walter Saide (16650807) 07 August 2023 (has links) <p>This dissertation describes the effects of a <i>de novo</i> mutation of CaMKII found in children with learning disabilities and describes its effect on catalytic activity. We develop a malachite green assay for the measurement of CaMKII activation and use it for high-throughput chemical screening to identify CaMKII inhibitors and enhancers. We also propose a new mechanism of regulation of CaMKII activity by ADP.</p><p><br></p> Cell neurochemistry Enzymes Basic pharmacology Biologically active molecules Biomolecular modelling and design Proteins and peptides Catalysis and mechanisms of reactions Reaction kinetics and dynamics CaMKII α learning and memory impairment calmodulin calcium signaling kinase activity medicinal chemistry molecular pharmacology enzyme kinetics western blotting biochemistry molecular modeling high throughput chemical screening assay development protein structure enzyme coupled assays malachite green assay cellular biology fluorescence microscopy hplc lc-ms/ms autophosphorylation ATP:ADP ratios

1

Page generated in 0.0879 seconds