Human Gene Set: BIOCARTA_IL12_PATHWAY

For the Mouse gene set with the same name, see BIOCARTA_IL12_PATHWAY

Standard name BIOCARTA_IL12_PATHWAY
Systematic name M4319
Brief description IL12 and Stat4 Dependent Signaling Pathway in Th1 Development
Full description or abstract Interleukin-12 (IL-12) promotes cell-mediated immunity by inducing Th1 cell differentiation and activation of both T cells and NK cells. Dendritic cells and macrophages in peripheral tissues act as antigen presenting cells and secrete IL-12 as one component of the antigen response, Th1 differentiation. The role of IL-12 in cellular immunity is largely mediated by the STAT-4 transcription factor. STAT-4 is essential for IL-12 activity and the phenotype of mice lacking STAT-4 is very similar to the phenotype of mice lacking the IL-12 receptor or IL-12. The role of IL-12 in Th1 differentiation may not be to induce the Th1 cell fate, but to stimulate growth of cells determined for the Th1 cell fate by the T-bet transcription factor. Several signaling pathways contribute to IL-12 activation of STAT-4 to regulate cell-mediated immune responses. The JAK kinases such as JAK2 and TYK2 interact with the activated IL-12 receptor and tyrosine phosphorylate the IL-12 receptor and STAT-4. IL-12 also activates a map kinase pathway activating the map kinase kinase MKK6 and p38. Phosphorylation of STAT-4 on serine 721 by p38 contributes to the full transcriptional activation of genes by STAT-4. Some of the events downstream of IL-12 appear to include genes activated indirectly by STAT-4, such as genes activated by the transcription factor ERM. ERM is in the Ets family of transcription factors, is activated by IL-12 and activates IL-12 inducible genes such as Interferon-gamma that are not activated by STAT-4 itself. Interferon-gamma transcription in T cells is also activated by other signals such as from the T cell receptor. Other proteins activated transcriptionally downstream of IL-12 and STAT-4 include the chemokine receptor CCR5 and IL-18 and its receptor. Some viruses, including HIV, repress cell-mediated immunity by blocking IL-12 signaling.
Collection C2: Curated
      CP: Canonical Pathways
            CP:BIOCARTA: BioCarta Pathways
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External links https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_il12Pathway.gif
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Source species Homo sapiens
Contributed by BioCarta
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identifier namespace		 Human_RefSeq
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Version history 7.0: Changed members. Upgraded to final version of Biocarta.


License Terms for BioCarta data in MSigDB

MSigDB gene sets derived from BioCarta pathways are protected by copyright, (c) 2000-2017 BioCarta, all rights reserved. They are provided under license to the Broad Institute, Inc. with qualified permission to include in this release, subject to Biocarta's "Disclaimer of Liability and of Warranties" (formerly found at www.biocarta.com). Inclusion of these gene sets is conditioned upon acknowledgment and retention of the aforementioned copyright, and agreement to such disclaimer. The BioCarta derived gene sets are in the MSigDB C2 and M2 collections, and can be recognized by the "BIOCARTA_" prefix in their name.

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