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Transcription factors of the STAT family are required for cellular responses to multiple signaling molecules. After ligand binding-induced activation of cognate receptors, STAT proteins are phosphorylated, hetero- or homodimerize, and translocate to the nucleus. Subsequent STAT binding to specific DNA elements in the promoters of signal-responsive genes(More)
Binding of interferons IFN-alpha and IFN-gamma to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators (or Stat proteins, for signal transducers and activators of transcription). Interferon-alpha activates both Stat91 (M(r) 91,000; ref. 1) and Stat113 (M(r) 113,000; ref. 2) whereas IFN-gamma(More)
To gain a better understanding of the role of DCC and Neogenin in neural and nonneural tissues during vertebrate development we have carried out in situ hybridization studies to determine their expression patterns throughout the mid to late stages of mouse embryogenesis. This analysis revealed striking contrasts in both the spatial and temporal expression(More)
Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, interleukin-11, and ciliary neurotrophic factor bind to receptor complexes that share the signal transducer gp130. Upon binding, the ligands rapidly activate DNA binding of acute-phase response factor (APRF), a protein antigenically related to the p91 subunit of the interferon-stimulated gene(More)
In the Drosophila embryo, a subset of muscles require expression and function of the RYK subfamily RTK gene derailed (drl) for correct attachment. We have isolated a second RYK homolog, doughnut (dnt), from Drosophila. The DNT protein exhibits 60% amino acid identity to DRL, and is structurally as similar to the mammalian RYK proteins as is DRL, indicating(More)
M-CSF/CSF-1 supports the proliferation and differentiation of monocytes and macrophages. In mice, CSF-1 also promotes proinflammatory responses in vivo by regulating mature macrophage functions, but little is known about the acute effects of this growth factor on mature human macrophages. Here, we show that in contrast to its effects on mouse bone(More)
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards(More)
BACKGROUND CYT997 is a novel microtubule inhibitor and vascular-disrupting agent with marked preclinical anti-tumour activity. METHODS This phase I dose-escalation study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of CYT997 administered by continuous intravenous infusion over 24 h every 3 weeks to patients with advanced solid(More)
  • A E Pond, M P Roach, M Sono, A H Rux, S Franzen, R Hu +8 others
  • 1999
UV-visible absorption and magnetic circular dichroism (MCD) data are reported for the cavity mutants of sperm whale H93G myoglobin and human H25A heme oxygenase in their ferric states at 4 degreesC. Detailed spectral analyses of H93G myoglobin reveal that its heme coordination structure has a single water ligand at pH 5.0, a single hydroxide ligand at pH(More)