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 34 for “"SH2 domain"”.
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Characterizing the Phosphorylation State of Tie2 using SH2 Domain Fusion Proteins
… downstream signaling via their Src homology 2 (SH2) domains. Currently there are no phosphospecific antibodies for Tie2, therefore, identifying critical residues responsible for certain pathways remains difficult. In our study, we aim to use purified SH2 domains of known binding partners to Tie2 …
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Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain
… pYEEI-derived peptidomimetic ligands to the Src SH2 domain were evaluated to investigate the effects of structural changes on protein-ligand binding energetics. The effect of preorganizing the pYEEI ligand into its binding conformation was analyzed by substituting the isoleucine residue with a …
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Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain
… of a conserved tyrosine in the Src homology 2 (SH2) domains of Src family kinases, which was frequently observed in human cancer specimens and regulated in cancer-derived cell lines. Using the Lyn SH2 domain as a model, I discovered that when this tyrosine (Y194) is phosphorylated, the domain …
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Disulfide Bridging the Gap between Src and Cortactin: A New Paradigm in SH2 Domain-mediated Signaling
… between Src and cortactin, whereby the Src SH2 domain interacts with cortactin via a disulfide bond formation and that this binding event is necessary for the formation of pro-invasive invadopodia. The work here also defines a paradigm shift in how SH2 domain-containing proteins interact …
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Synthetic Studies on Small Molecule Modulators of Src Homology 2 (SH2) Domain-Containing Inositol 5’-Phosphatase (SHIP)
<p>Small molecule modulators of SH2-containing inositol 5’-phosphatase (SHIP) have recently become a hotly pursued area in medicinal chemistry. Pharmaceutical targeting of SHIP with small molecules has been identified as a new method to directly influence the phosphoinositide 3-kinase (PI3K) cell …
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Synthesis of [beta]-heteroaryl propionates via trapping of carbocations with [pi]-nucleophiles, efforts towards the total synthesis of acutumine, and the design, synthesis, and thermodynamics of protein-ligand interactions at the Src SH2 domain
… binding affinity of various ligands to the Src SH2 domain was also investigated. A series of four ligands were designed and enantioselectively synthesized in order to compare how differences in the conformations of the ligands affect the thermodynamics of binding. Namely, cyclopropanes were …
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Specificity of SH2 domains and protein tyrosine phosphatases
… (PTKs) or have an associated PTK activity. SH2 domains and protein tyrosine phosphatases (PTPs) play essential roles in transmitting these signals. SH2 domains are small domains of V100 amino acids that bind to phospho-tyrosine (pY) in the context of adjacent amino acids. and PTPs counteract …
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A strategy to suppress STAT1 signalling conserved in pathogenic poxviruses and paramyxoviruses
… of 018. Mapping experiment identified the SH2 domain of STAT1, a region important for STAT1 recruitment to IFN-receptors, as the site of 018 binding. In cells expressing 018, STAT1 failed to be phosphorylated, thereby preventing STAT1 activation. Taking the type II IFN pathway as a model, …
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Mutations In Stat3 Associated With Human Hyper Ige Syndrome Enhance Nfκb and Mapk-Mediated Gene Expression
… with mutations in STAT3, which disrupt protein domains responsible for transcriptional function. Patients with HIES display osteoporosis and enhanced inflammatory cytokine production similar to hematopoietic Stat3-deficient mice. Since osteoclast and inflammatory cytokine genes are NFκB targets, …
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FRK cancer-related mutations: Effect on enzymatic activity and cellular processes
… results where the mutations in kinase domain (K265R, N359I, del VF) reduced, inactivated and increased kinase activity respectively. Proliferation, migration and invasion assays were also performed with the R64P, K265R, N358I and VF mutations. The proliferation data revealed that the …
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Protein/Peptide Recognition Modules in Cellular Signaling and HIV Pathogenesis
<p>The peptide-recognition domains play a key role in Eukaryotic signal transduction by mediating sequence-specific interactions with their protein/peptide ligands. In this thesis, I illustrate in molecular detail the recognition mechanisms utilized by three peptide-recognition domains: SH2 (Src …
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Post-translationally Modified Glucocorticoid Receptors and Protein Tyrosine Kinase 6 Modulate Triple Negative Breast Cancer Phenotypes
… we created kinase-dead (KM) and kinase-intact domain structure mutants of PTK6 via in frame deletions of the N-terminal SH3 or SH2 domains. While the PTK6 kinase domain contributed to soft-agar colony formation, PTK6 kinase activity was entirely dispensable for cell migration. Specifically, …
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Insulin Receptor Substrate-1 Serine Phosphorylation by a Novel Phosphatidylinositol-3'-Kinase-Associated Serine Kinase Regulates Insulin and Interferon Receptor Signaling
… subunit of PI 3-kinase through src homology 2 (SH2) domain interactions and can serine phosphorylate IRS-1 after insulin stimulation. More importantly, PAS kinase mediated IRS-1 serine phosphorylation reduced subsequent tyrosine phosphorylation of IRS-1 by insulin receptors (IRs). Finally, under …
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Studies on the Leukocyte-Associated Ig-Like Inhibitory Receptor-1 Signaling Pathway in T Lymphocytes
… whether the LAIR-1 signaling complex contains SH2 domain-containing phosphatase (SHP)-1, SHP-2, C-terminal src kinase (Csk), and/or the protein tyrosine phosphatase, non-receptor 22 (PTPN22), whether these phosphatases are activated upon LAIR-1 and its ligand interaction, and whether SHP1 plays …
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Systematic Identification of Interaction Partners of RET Receptor Isoforms
… Two-Hybrid (MaMTH) assay using a library of SH2 domain-containing adaptor and signaling proteins, to screen for interactions with each RET isoform. Through different steps of analysis of MaMTH screen data, we narrowed down RET potential interactors. We complemented these studies by ranking …
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UNIQUE ALLOSTERIC MECHANISM REGULATING PROTEIN-PROTEIN INTERACTION THROUGH PHOSPHORYLATION: A CASE STUDY OF THE CONFORMATIONAL CHANGES IN THE SYK TANDEM SH2 PROTEIN
… Syk is a 72-kDa kinase comprising three folded domains: two SH2 domains and a catalytic domain. The tandem SH2 domains connected by linker A are key to the regulation of Syk activity. Immune signaling through Syk is initiated by the binding of the tandem SH2 to the dpITAMs found on immune cell …
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The 5' inositol phosphatase SHIP2 regulates EGF-elicited protrusion in MTLn3 cells
… epithelial isoform, Menalla, is downregulated. SH2- domain containing 5-inositol phosphatase (SHIP2) interacts with Mena and is thought to play a role in breast cancer. SHIP2 is a 5-phosphatase that catalyzes the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P 3) to …
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Effects of mutant SHP2 expression on heart function in Duchenne muscular dystrophy
… adolescence and progresses to heart failure. SH2 domain-containing tyrosine phosphatase 2 (SHP2) plays a regulatory role in several cell signaling events. Work from our lab has discovered that a loss-offunction mutation in SHP2 improves heart function after transverse aortic banding. I …
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Investigating FAM83H, a protein mutated in Amelogenesis Imperfecta
… family is related by a conserved N-terminal domain of unknown function, DUF1669. Beyond the DUF1669 domain, no other functional domains have been identified within FAM83 proteins. Although the DU1669 domain has a phospholipase-D-like catalytic motif, no phospholipase-D-like catalytic activity …
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The Functional Analysis of A Major Tyrosine Phosphorylation Site On Actin
… or ‘readers’, for this modification. Using an SH2 (Src Homology 2) protein domain array, we identify N-terminal SH2 domains of p85, regulatory subunits of Phosphatidylinositol 3-kinase (PI3K), and VAV2, a Rho GTPase guanine nucleotide exchange factor, as phosphorylation-dependent binding …
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