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Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular(More)
Myeloproliferative disorders are clonal haematopoietic stem cell malignancies characterized by independency or hypersensitivity of haematopoietic progenitors to numerous cytokines. The molecular basis of most myeloproliferative disorders is unknown. On the basis of the model of chronic myeloid leukaemia, it is expected that a constitutive tyrosine kinase(More)
We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally regulated genes - all linked to over 5,500 published articles.(More)
We show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression. This interaction is specific as JAK1 has no effect. Residues 32 to 58 of the JAK2 JH7 domain are required for EpoR surface expression. Alanine scanning(More)
Drosophila Mad proteins are intracellular signal transducers of decapentaplegic (dpp), the Drosophila transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP) homolog. Studies in which the mammalian Smad homologs were transiently overexpressed in cultured cells have implicated Smad2 in TGF-beta signaling, but the physiological relevance of(More)
We report that the erythropoietin receptor cytosolic juxtamembrane region is conformationally rigid and contains a hydrophobic motif, composed of residues L253, I257, and W258, that is crucial for Janus kinase 2 (JAK2) activation and receptor signaling. Alanine insertion mutagenesis shows that the orientation of this motif and not its distance from the(More)
A previously cloned cDNA encodes one subunit of the human interferon alpha/beta receptor (IFN alpha R), denoted IFN alpha R1. To study the expression and signaling of IFN alpha R1, we used monoclonal antibodies (mAbs) generated against the baculovirus-expressed ectodomain of IFN alpha R1. Immunoprecipitation and immunoblotting of lysates from a variety of(More)
During the past 10 years, major progress has been accomplished with the discovery of activating mutations that are associated with the vast majority of BCR-ABL negative human myeloproliferative neoplasms (MPNs). The identification in 2005 of JAK2 V617F triggered great interest in the JAK2-STAT5/STAT3 pathway. Discovery in 2006 of mutants of thrombopoietin(More)
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature blood cells. In the majority of classic MPN--polycythemia vera, essential thrombocythemia, and primitive myelofibrosis--driver oncogenic mutations affecting Janus kinase 2 (JAK2) or MPL lead to constitutive activation of cytokine-regulated intracellular(More)
Binding of erythropoietin (Epo) to the Epo receptor (EpoR) is crucial for production of mature red cells. Although it is well established that the Epo-bound EpoR is a dimer, it is not clear whether, in the absence of ligand, the intact EpoR is a monomer or oligomer. Using antibody-mediated immunofluorescence copatching (oligomerizing) of epitope-tagged(More)