Mechanisms of type I interferon signaling in normal and malignant cells.
Type I interferons (IFNs) are cytokines that induce multiple biological effects on target cells, including antiviral, antiproliferative, and immunomodulatory activities. Consistent with the pleiotropic nature of these cytokines, multiple signaling pathways are activated during binding of IFNs to the type I IFN receptor. An important signaling cascade activated by type I IFNs is the Jak-Stat pathway. Activation of the Tyk-2 and Jak-1 kinases, and downstream formation of various Stat complexes, mediates IFN-dependent gene transcription for IFN-stimulated genes. In addition to the classic Jak-Stat pathway, type I IFNs activate multiple other pathways, including the insulin receptor substrate-phosphatidylinositol 3'-kinase cascade, the CBL-CrkL pathway, and mitogen-activated protein kinase pathways. There is accumulating evidence that non-Stat IFN-regulated signaling pathways play important roles in the generation of the antiproliferative effects of type I IFNs. In this review, the regulation of various signaling cascades by the type I IFN receptor is summarized and an update on recent advances in the field is provided.
Li
Yongzhong
Y
Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School and Lakeside Veterans, Administration Medical Center, Chicago, IL 60611, USA.
Srivastava
Kishore K
KK
Platanias
Leonidas C
LC
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000378:metabolism*; D053613:Janus Kinase 1; D009369:Neoplasms / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases