Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 25 for “"Activation loop"”.
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Structural Analysis of STE20-Related Proline-Alanine-Rich Kinase (SPAK)
… two dimer interfaces. One is from the unique activation loop-swapped structure. The other is formed between the N-terminal domain of one molecule and the C-terminal domain of the second molecule. Comparison the structure with unphosphorylated inactive OSR1 revealed significant conformational …
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Mutagenic Studies of RdoA, a Eukaryotic-Like SER/THR Protein Kinase in Salmonella Enterica Serovar Typhimurium
… regulate activity through phosphorylation of an activation loop. Although RdoA does not contain a canonical activation loop, its carboxyl terminus is proposed to play a similar regulatory function. Mutations of a putative autophosphorylation target in the carboxyl terminus resulted in loss of in …
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Regulation and Dysregulation via Docking Interactions in WNK and ERK1/2 MAPK Signaling
… on understanding the role of SPAK and OSR1 activation loop domain-swapping. I solved the structure of the inactive SPAK kinase domain, and utilized a previously identified dimerization blocking mutation to probe the role of SPAK dimerization on activation and activity. I determined that SPAK …
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Nuclear Behaviors of ERK1/2 Signaling
… to the classically defined phosphorylation activation loop sites. To test the possibility that alternate phosphorylation inputs affect ERK2 in ways other than its kinase activity, I utilized phospho-mimetic mutants to assay oligonucleotide binding. I demonstrated that phosphorylation on the …
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Discovery of novel highly selective Rho kinase (ROCK) inhibitory peptides and evaluation of their biological activities
… modeling. It was identified to be on the activation loop, a novel locus for designing a new class of inhibitory drugs. Furthermore, alanine scanning and synthesized truncated mutants of Peptide25 were used to identify amino acids critical for ROCK1’s activation loop binding. This binding …
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Autoinhibition and Chloride Sensing in the WNK1 Kinase
… associated with the regulation of CCCs via the activation of the WNK1 substrates OSR/SPAK. Prior investigation of the system has demonstrated that CCCs are activated by increasing con- centrations of extracellular salt and by intracellular phosphorylation from the OSR/SPAK kinases. Due to it …
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The Mechanism of Activation of Potassium Dependent and Potassium Independent Asparaginases from Common Bean (Phaseolus vulgaris)
… that PvAspG1 requires potassium for catalytic activation and crystal structure analysis suggested that Ser-118 in the activation loop plays a critical role in alkali metal coordination. This amino acid residue is replaced by an isoleucine in PvAspG-T2. Reciprocal mutants of the enzymes were …
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Regulation of Protein Kinases (Syk and PKC zeta) in platelets
… receptor systems leads to alpha IIb beta 3 activation, thromboxane generation, ADP release, etc., culminating in platelet clot or thrombus formation. The protein kinase family of enzymes mediates a significant number of these intracellular signaling events that culminate in platelet …
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With No Lysine (WNK) Family Proteins and Their Interaction with Downstream Kinases
… sites of OSR1 reveals multiple sites along the activation loop that can promote increased activation if carrying a negative charge. It is unknown if these sites are phosphorylated in vivo. However, a second site of WNK1 phosphorylation just outside of the OSR1 kinase domain does not seem to …
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Molecular Mechanisms Underlying Innate Immune Kinase TBK1-Driven Oncogenic Transformation
… of host defense mechanisms. The pathological activation of TBK1 in cancer can overcome programmed cell death cues, enabling cells to survive oncogenic stress. The mechanistic basis of TBK1 prosurvival signaling, however, has been enigmatic. Here we show that TBK1 directly activates AKT by …
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Structure of the LKB1-STRAD-MO25 tumour suppressor complex
… stabilised by MO25 interacting with the LKB1 activation loop. This represents a previously undescribed mechanism of kinase activation that may be relevant to understanding the evolution of other pseudokinases. Finally the structure of the LKB1 heterotrimer reveals how mutations found in …
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Characterization of the Type III Effector VOPA from Vibrio Parahaemolyticus
… that YopJ acetylates MKKs and inhibits kinase activation by blocking phosphorylation (1). The molecular characterization of VopA has focused on its effect on signaling pathways. In contrast to YopJ, VopA only inhibits MAPK signaling and shows no effect on the NFκB pathway in mammalian cells. In …
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The localisation and regulation of phosphatidylinositol-4-phosphate 5-Kinase gamma splice variants and the discovery of a new mammalian splice variant, PIP5KIγ_v6
… 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 …
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Global characterization of oncogenic kinase signaling
Aberrant activation and expression of the proto-oncogene Src have been observed in various human malignancies. Despite major advancements in kinase-targeted cancer therapies, targeting Src has only achieved limited clinical success, thus highlighting the urgent need to better understand the complex …
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The Role of IKKβ in Osteoclastogenesis and Inflammatory Osteolysis
… Heightened osteoclast differentiation and activation in these conditions causes bone loss which results in increased fracture risk, bone pain, and deformity. Understanding the mechanisms by which osteoclasts develop will elucidate important targets for therapy in these conditions. …
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Inhibition of AMPK via phosphorylation at Ser485/491: multiple mechanisms of regulation
… SAMS peptide assay) and phosphorylation of its activation loop at Thr172, we observed increased muscle glycogen, phosphorylation of AMPK’s α1/α2 subunit at Ser485/491, and PP2A activity, and decreased SIRT1 expression, all of which have been shown to diminish AMPK activity. Dysregulation of one …
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Lariat peptide inhibitors of Abl kinase
… by the activating mutations located in the activation loop of kinase, and instead bind preferentially to the kinase active conformation. Selectivity analysis indicated that the lariats do not recognize Src family kinases, which share a high structural similarity with Abl kinase in their …
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LKB1 signaling pathways in adipocytes - Focus on the AMPK-related kinase SIK2
… a specific threonine residue in their activation loop. The aim of this thesis was to investigate the regulation of LKB1 signaling pathways in adipocytes, with a focus on SIK2, which is of particulate interest in adipocytes due to its high abundance in these cells. We show that AMPK …
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Diverse functions of LanC-like proteins in mammalian cells
… acids containing peptides that mimic the activation loop of Erk and Akt protein kinases were synthesized. LanCL proteins were shown to add GSH to these dehydroamino acids containing peptides. The same C-glutathionylation was also observed by using dehydroamino acid containing proteins as …
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Computational investigation of early events in plant growth signaling
… BRI1-BAK1 association and activation. First, we examine the brassinosteroid-induced association of the BRI1 and BAK1 extracellular domains. Using a replica exchange umbrella sampling scheme together with alchemical free energy calculations and conventional molecular dynamics …
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