IL12*

Protein IL12*

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_EXPRESSION

References
NATURAL_KILLER
CASCADE:TGFB
CASCADE:TLR2_4
CASCADE:IL12
CASCADE:CSF2
CASCADE:IL4
PMID:12244147, PMID:24204259
IL4 via IL-4R type I JAK3 and STAT6 (but not IL13) upregulates production of IL12p70
PMID:15546391
Interleukin (IL)-12 is a heterodimeric cytokine composed of two disulfide-linked subunits, p35 and p40.
This cytokine is produced by a variety cells including monocytes, neutrophils, and B cells, but the major producers of IL-12 are macrophages and dendritic cells (DCs).
The IL-12 receptor (IL-12R) is composed of two subunits termed ??1 and ??2, which are structurally related to the type I cytokine receptor superfamily (44???47). The affinity of IL-12 for either subunit alone is low, but coexpression of both ??1 and ??2 subunits generates human IL-12 high-affinity binding sites. IL-12p40 interacts predominantly with the ??1 subunit, whereas p35 interacts largely with the ??2 subunit.
PMID:8700208
IL-12 signaling induces STAT4 tyrosine phosphorylation. And induces IFNG production,
probably via STAT4.
PMID:12372421
The human perforin gene is a direct target of STAT4 activated by IL-12 in NK cells
PMID:22077060
Prolonged and repeated IL-12 stimulation may also activate an additional negative feedback mechanism to control and terminate the IL-12???induced proinflammatory immune response, representing a unique example of cytokine signaling auto-regulation.
The miRs-132, 212, and 200a were shown to be induced in human NK cells by IL-12 stimulation, which in turn target STAT4 mRNA, thereby providing a negative regulatory pathway for IL-12 signaling.
PMID:8683106
IL-12 induced phosphorylation of JAK2 and TYK2 in both preactivated primary NK and NK3.3 cells.
PMID:9834059
NK cells stimulated by IL12 ??accumulate much higher levels of the IL-12Rbeta2-chain mRNA and are significantly more responsive to IL-12 than??NK2??cells??at the level of activation of STAT4 transcription factor
PMID:21042762
Inhibition of TGF-?? signalinginduced phenotypic maturation of BM-DCs and human DCs and improved their abilities to produce IL-12 in a dose-dependent manner via SMADs.
NK cells stimulated by IL12 induces IL10 production.

IL12*@default

References
in_re428( Innate Immunity ):
PMID:20547845
TLR4 signaling downstream of HMGB1 induces secretion of IL10
in_re1234( Innate Immunity ):
CASCADE:IL15
CASCADE:IL21
CASCADE:IL12
NATURAL_KILLER

Modifications:
In compartment: INNATE_IMMUNE_CELL_Cytosol

IL12*@INNATE_IMMUNE_CELL_Cytosol

In compartment: default

IL12*@default

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Membrane

IL12*:IL12RB1:IL12RB2:JAK2|pho:TYK2|pho@INNATE_IMMUNE_CELL_Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: