IL12 Signaling Pathway

Preferred Label : IL12 Signaling Pathway;

NCIt related terms : IL12 and Stat4 Dependent Signaling Pathway in Th1 Development;

Alternative definition : BIOCARTA: 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. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_IL12Pathway;

Details

Origin ID

C39117;

UMLS CUI

C1512588;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- C-C Chemokine Receptor Type 5 [NCIt concept]
- C-X-C Chemokine Receptor Type 3 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 [NCIt concept]
- ETS Translocation Variant 5 [NCIt concept]
- Interferon Gamma [NCIt concept]
- Interleukin-12 Receptor Subunit Beta-1 [NCIt concept]
- Interleukin-12 Receptor Subunit Beta-2 [NCIt concept]
- Interleukin-12 Subunit Alpha [NCIt concept]
- Interleukin-12 Subunit Beta [NCIt concept]
- Interleukin-18 [NCIt concept]
- Interleukin-18 Receptor 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Non-Receptor Tyrosine-Protein Kinase TYK2 [NCIt concept]
- Signal Transducer and Activator of Transcription 4 [NCIt concept]
- T-Cell Surface Glycoprotein CD3 Delta Chain [NCIt concept]
- T-Cell Surface Glycoprotein CD3 Epsilon Chain [NCIt concept]
- T-Cell Surface Glycoprotein CD3 Gamma Chain [NCIt concept]
- T-Cell Surface Glycoprotein CD3 Zeta Chain [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Tyrosine-Protein Kinase JAK2 [NCIt concept]
pathway_has_gene_element
- CCR5 wt Allele [NCIt concept]
- CD247 wt Allele [NCIt concept]
- CD3D wt Allele [NCIt concept]
- CD3E wt Allele [NCIt concept]
- CD3G wt Allele [NCIt concept]
- CXCR3 wt Allele [NCIt concept]
- ETV5 wt Allele [NCIt concept]
- IFNG wt Allele [NCIt concept]
- IL12A wt Allele [NCIt concept]
- IL12B wt Allele [NCIt concept]
- IL12RB1 wt Allele [NCIt concept]
- IL12RB2 wt Allele [NCIt concept]
- IL18 wt Allele [NCIt concept]
- IL18R1 wt Allele [NCIt concept]
- JAK2 wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- MAP2K6 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- STAT4 wt Allele [NCIt concept]
- TYK2 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

You can consult :

recommendations
documents concerning education
documents for patients