Topic
JAK-STAT signaling pathway
About: JAK-STAT signaling pathway is a research topic. Over the lifetime, 3581 publications have been published within this topic receiving 257581 citations.
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TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.
7,056 citations
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Abstract: Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.
5,746 citations
TL;DR: Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses.
4,628 citations
TL;DR: This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction, with emphasis on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins.
Abstract: The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.
3,050 citations
TL;DR: It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance current thinking about how interferons work.
Abstract: Interferons are cytokines that have antiviral, antiproliferative and immunomodulatory effects. Because of these important properties, in the past two decades, major research efforts have been undertaken to understand the signalling mechanisms through which these cytokines induce their effects. Since the original discovery of the classical JAK (Janus activated kinase)-STAT (signal transducer and activator of transcription) pathway of signalling, it has become clear that the coordination and cooperation of multiple distinct signalling cascades - including the mitogen-activated protein kinase p38 cascade and the phosphatidylinositol 3-kinase cascade - are required for the generation of responses to interferons. It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance our current thinking about how interferons work.
2,912 citations