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Cytokines are secreted proteins that regulate important cellular responses such as proliferation and differentiation. Key events in cytokine signal transduction are well defined: cytokines induce receptor aggregation, leading to activation of members of the JAK family of cytoplasmic tyrosine kinases. In turn, members of the STAT family of transcription(More)
A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including(More)
Functional expression cloning strategies are highly suitable for the analysis of the molecular control of apoptosis. This approach has two critical advantages. Firstly, it eliminates prior assumptions about the properties of the proteins involved, and, secondly, it selectively targets proteins that are causally involved in apoptosis control and which affect(More)
We have combined retroviral expression cloning with random mutagenesis to identify two activating point mutations in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 by virtue of their ability to confer factor independence on the haemopoietic(More)
The high-affinity receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are heterodimeric complexes consisting of cytokine-specific alpha subunits and a common signal-transducing beta subunit (hbetac). We have previously demonstrated the oncogenic potential of this group of receptors by identifying(More)
The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMRalpha) and a common signal-transducing beta-subunit (hbetac) that is shared with the interleukin-3 and -5 receptors. We have previously identified a constitutively active extracellular point mutant of hbetac,(More)
A previous study using random mutagenesis identified an activating mutation in the common beta subunit (hbetac) of the human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5 receptors in which an isoleucine residue (Ile374) in the extracellular region of hbetac is replaced by asparagine (Jenkins, B. J., D'Andrea, R., and(More)
In the hair follicle the cuticle develops as a thin layer of cells between the hair shaft cortex and the inner root sheath. Once the cuticle cells begin to differentiate they accumulate cysteine-rich granules in their cytoplasm but the identity of their constituent proteins has remained largely an enigma. In this report we show differential expression of a(More)
Two-hundred and twenty-eight patients admitted to a District General Hospital Coronary Care Unit with a confirmed myocardial infarction were given a detailed information session by nurses. Information included a detailed programme of exercise during convalescence and attitudes toward diet, smoking and sexual intercourse. Patients were asked to assess the(More)