4.3 Article

A network map of Interleukin-10 signaling pathway

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SPRINGER
DOI: 10.1007/s12079-015-0302-x

关键词

Co-stimulatory molecules; Interferon-gamma (IFN-gamma); Lipopolysaccharides; Pro-inflammatory cytokines; Protein-protein interactions; Translocation; NetSlim; Systems biology markup language

资金

  1. Department of Biotechnology (DBT), Government of India
  2. Infosys Foundation
  3. University Grants Commission (UGC), Government of India
  4. Indian Council of Medical Research (ICMR), Government of India
  5. Council of Scientific & Industrial Research (CSIR), Government of India
  6. DST-IDP research grant on Development of epitope based diagnostic gadget for detection of Mycobacterium tuberculosis in the Indian population from the Department of Science Technology, Government of India [IDP/MED/2011/23]

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Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions. It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages. In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling. IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer. In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host. The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking. To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature. The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation. In all, 37 molecules and 76 reactions were annotated. The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group.

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