Comprehensive network map of interferon gamma signaling

Abstract

Interferon gamma (IFN-γ), is a cytokine, which is an important regulator of host defense system by mediating both innate and adaptive immune responses. IFN-γ signaling is primarily associated with inflammation and cell-mediated immune responses. IFN-γ is also represented as antitumor cytokine which facilitates immunosurveillance in tumor cells. In addition, IFN-γ mediated signaling also elicits pro-tumorigenic transformations and promotes tumor progression. Impact of IFN-γ signaling in mammalian cells has been widely studied which indicate that IFN-γ orchestrates distinct cellular functions including immunomodulation, leukocyte trafficking, apoptosis, anti-microbial, and both anti- and pro-tumorigenic role. However, a detailed network of IFN-γ signaling pathway is currently lacking. Therefore, we systematically curated the literature information pertaining to IFN-γ signaling and develop a comprehensive signaling network to facilitate better understanding of IFN-γ mediated signaling. A total of 124 proteins were catalogued that were experimentally proven to be involved in IFN-γ signaling cascade. These 124 proteins were found to participate in 81 protein-protein interactions, 94 post-translational modifications, 20 translocation events, 54 activation/inhibiton reactions. Further, 236 differential expressed genes were also documented in IFN-γ mediated signaling. IFN-γ signaling pathway is made freely available to scientific audience through NetPath at ( http://www.netpath.org/pathways?path_id=NetPath_32 ). We believe that documentation of reactions pertaining to IFN-γ signaling and development of pathway map will facilitate further research in IFN-γ associated human diseases including cancer.

Keywords: Interferon gamma receptor; Interferon response factors; Interferon-gamma activated sequence and PathVisio; Signal transducer and activator of transcription.

Fig. 1

A graphical representation of IFN-γ signaling pathway. The pathway map represents reactions of IFN-γ signaling pathway that are documented in NetPath. Different types of reactions and molecules are distinguished with different colors and arrows as provided in the legend. Solid arrows represent direct reactions and a dashed arrow represents reactions whose mechanisms are currently unknown. Post-translational modifications with site and residues are also provided in the map