John E. Ladbury

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ular mechanisms for the high selectivity of these peptides for the)..l-and 0-opioid receptors in light of NMR conformational analysis. The extensive similarities between prepro regions of precursor5 encoding these peptides. Jennaseptins and other peptides with different structure and biological activity from various amphibian specie~ are also discmsed. The(More)
Constitutive receptor tyrosine kinase phosphorylation requires regulation of kinase and phosphatase activity to prevent aberrant signal transduction. A dynamic mechanism is described here in which the adaptor protein, growth factor receptor-bound protein 2 (Grb2), controls fibroblast growth factor receptor 2 (FGFR2) signaling by regulating receptor kinase(More)
The SH2 and SH3 domain structural integrity and functionality were confirmed by peptide binding assays. Binding studies using two phosphotyrosine peptides derived from EGFR (FLPVPE{pY}IN-QSVPKR) and Shc (EEPPDHQ{pY}YNDFPGK) for the Grb2 SH2 domain and a SOS1-derived proline-rich peptide (PVPPPVPPRRRPEY) for the SH3 domains were performed using MST 1. Grb2(More)
Members of the plakophilin-catenin sub-family (Pkp-1, -2, and -3) facilitate the linkage of desmosome junctional components to each other (e.g. desmosomal cadherins to desmoplakin) and the intermediate-filament cytoskeleton. Pkps also contribute to desmosomal stabilization and the trafficking of its components. The functions of Pkps outside of the desmosome(More)
Isothermal titration calorimetry (ITC) provides highly complementary data to high-resolution structural detail. An overview of the methodology of the technique is provided. Ultimately, the correlation of the thermodynamic parameters determined by ITC with structural perturbation observed on going from the free to the bound state should be possible at an(More)
LiaR is a 'master regulator' of the cell envelope stress response in enterococci and many other Gram-positive organisms. Mutations to liaR can lead to antibiotic resistance to a variety of antibiotics including the cyclic lipopeptide daptomycin. LiaR is phosphorylated in response to membrane stress to regulate downstream target operons. Using DNA(More)
To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances(More)
The adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions. Grb2 plays a pivotal role in tyrosine kinase-mediated signal transduction including linking receptor tyrosine kinases to the Ras/mitogen-activated protein (MAP) kinase pathway,(More)
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