Search results for IL12B

Showing 23 results out of 33

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Protein (5 results from a total of 5)

Identifier: R-HSA-447181
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: IL12B: P29460
Identifier: R-HSA-8950359
Species: Homo sapiens
Compartment: Golgi lumen
Primary external reference: UniProt: P29460
Identifier: R-HSA-8950126
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Primary external reference: UniProt: P29460
Interleukin-12 subunit beta have to be in the reticuum where it suffers processing by the PDI enzyme if it is going to homodimerize or heterodimerize with other subunits as Interleukin-23 alpha subunit (PMID:15720785)
Identifier: R-HSA-8950675
Species: Homo sapiens
Compartment: late endosome lumen
Primary external reference: UniProt: P29460
Identifier: R-HSA-8950760
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P29460

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6784999
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000113302

Reaction (5 results from a total of 12)

Identifier: R-HSA-8950456
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Murine cells have been shown to produce Interleukin-12 homodimer (IL-12p80) (Gillessen et al. 1995). In a cell-free system porcine Interleukin 12 homodimer (IL-12p80) is formed from two subunits of Interleukin 12 subunit beta (IL12B, IL-12p40), stabilized by a disulfide link. The cysteine in position 197 of IL12B is required for homodimer formation. Prolyl 4-hydroxylase subunit beta (P4HB), in this article referred to as protein disulfide isomerase (PDI), can act as a chaperone to induce homodimer formation (Martens et al. 2000). Human cells do not produce IL-12p80 under normal conditions (Ling et al. 1995), when however expressed acts as an antagonist of Interleukin-12 signaling, competing with the Interleukin 12 heterodimer (IL12) for its receptor (Ling et al. 1995).
Identifier: R-HSA-8950183
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Interleukin 23 subunit alpha (IL23A, IL23-p19) and Interleukin 12 subunit beta (IL12B, IL-12p40) bind to form the Interleukin-23 (IL23) heterodimeric complex (IL23A:IL12B). When 293T cells were transfected with IL23A only a small amount of protein could be immunoprecipitated from the supernatant, while protein was readily detected in cellular lysates, indicating inefficient secretion. Co expression of IL23A with IL12B enhanced secretion of IL23 (Oppmann et al. 2000). Moreover there is a disulfide bridge within IL12A which is necessary fro IL12B-induced secretion. Protein disulfide isomerases enable the formation of these bridges (Reitberger et al. 2017).
Identifier: R-HSA-8950113
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
The Interleukin-12 heterodimer (IL-12) is formed by Interleukin-12 subunit alpha (IL12A, IL-12p35) and Interleukin-12 subunit beta (IL12B, IL-12p40) (Podlaski et al. 1992, Kobayashi et al. 1989, Stern et al.1990). Heterodimerization occurs due to charged residue interactions (Yoon et al. 2000) and is stabilized by disulfide bounding.
IL12 heterodimerization is believed to occur in the endoplasmic reticulum (ER) because inhibition of the enzyme Prolyl 4-hydroxylase subunit beta (P4HB), referred to in this article as Protein disulfide isomerase (PDI), by bacitracin causes IL-12 retention in the ER (Alloza & Vandenbroek 2005).
Identifier: R-HSA-8950179
Species: Homo sapiens
Compartment: cytosol, extracellular region
Interleukin-12 subunit beta (IL12B, IL12p40) is secreted to the extracellular region.
Celecoxib and the 4-trifluoromethyl analogue of celecoxib (TFM-C) inhibit secretion of Interleukin-23, a dimer of Interleukin-23 subunit alpha (IL23A) and IL12B but do not affect the secretion of monomeric IL12B (McLaughlin et al. 2010).

This is a Black box event because the mechanism of IL12B secretion is unknown.
Identifier: R-HSA-8950410
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen, extracellular region
Interleukin-12 subunit beta (IL12B, IL-12p40) can form oligomers with other interleukin subunits or be secreted as a monomer to the extracellular region (Ling et al. 1995).
Production of human IL12B homodimers has only been detected in cells with IL-12p40 expression constructs (Ling et al 1995, Alloza & Vandenbroeck 2015), not in natural conditions (Carra et al 2000).

Complex (5 results from a total of 8)

Identifier: R-HSA-8950275
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Interleukin-23 heterodimer is formed by Interleukin-23 subunit alpha (IL23p19 or p19 or IL23A) and Interleukin-12 subunit beta (IL12B or p40 or IL12p40). Binding of p19 to p40 is mediated primarily by an arginine residue on helix D of p19 that forms an extensive charge and hydrogen-bonding netwrok with residues at the base of a pocket on p40. (PMID: 18680750) This dimer can be retained in the Endoplasmic reticulum upon TFM-C (4-trifluoromethyl-celecobix) treatment (PMID:20054003)
Identifier: R-HSA-447217
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-8950116
Species: Homo sapiens
Compartment: plasma membrane
Transfected COS cells express the Interleukin-12 receptor subunit both as monomers, and the dimerization or oligomerization of both receprots does not depend on Interleukin-12 binding. Anyway if Interleukin-12 is prebound to these cells, the resulting banding pattern does not change (PMID:7911493)
Identifier: R-HSA-8981056
Species: Homo sapiens
Compartment: cytosol
Transfected COS cells express the Interleukin-12 receptor subunit both as monomers, and the dimerization or oligomerization of both receprots does not depend on Interleukin-12 binding. Anyway if Interleukin-12 is prebound to these cells, the resulting banding pattern does not change (PMID:7911493)
Identifier: R-HSA-8950640
Species: Homo sapiens
Compartment: extracellular region
Homodimeric protein of Interleukin-12 beta subunit (IL12B or IL12p40) can be secreted to exert its inhibitory function over Interleukin-12 heterodimer interleukin-12 receptor interaction. The secretion has been shown experimentally in COS cells and by mean of ELISA assays (PMID: 7527811).

Set (2 results from a total of 2)

Identifier: R-HSA-6784990
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8937649
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (5 results from a total of 5)

Identifier: R-HSA-5607761
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
In addition to the activation of canonical NF-kB subunits, activation of SYK pathway by Dectin-1 leads to the induction of the non-canonical NF-kB pathway, which mediates the nuclear translocation of RELB-p52 dimers through the successive activation of NF-kB-inducing kinase (NIK) and IkB kinase-alpha (IKKa) (Geijtenbeek & Gringhuis 2009, Gringhuis et al. 2009). Noncanonical activity tends to build more slowly and remain sustained several hours longer than does the activation of canonical NF-kB. The noncanonical NF-kB pathway is characterized by the post-translational processing of NFKB2 (Nuclear factor NF-kappa-B) p100 subunit to the mature p52 subunit. This subsequently leads to nuclear translocation of p52:RELB (Transcription factor RelB) complexes to induce cytokine expression of some genes (C-C motif chemokine 17 (CCL17) and CCL22) and transcriptional repression of others (IL12B) (Gringhuis et al. 2009, Geijtenbeek & Gringhuis 2009, Plato et al. 2013).
Identifier: R-HSA-5676590
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
In addition to the activation of canonical NF-kB subunits, activation of SYK pathway by Dectin-1 leads to the induction of the non-canonical NF-kB pathway, which mediates the nuclear translocation of RELB-p52 dimers through the successive activation of NF-kB-inducing kinase (NIK) and IkB kinase-alpha (IKKa) (Geijtenbeek & Gringhuis 2009, Gringhuis et al. 2009). Noncanonical activity tends to build more slowly and remain sustained several hours longer than does the activation of canonical NF-kB. The noncanonical NF-kB pathway is characterized by the post-translational processing of NFKB2 (Nuclear factor NF-kappa-B) p100 subunit to the mature p52 subunit. This subsequently leads to nuclear translocation of p52:RELB (Transcription factor RelB) complexes to induce cytokine expression of some genes (C-C motif chemokine 17 (CCL17) and CCL22) and transcriptional repression of others (IL12B) (Gringhuis et al. 2009, Geijtenbeek & Gringhuis 2009, Plato et al. 2013).
Identifier: R-HSA-447115
Species: Homo sapiens
Interleukin-12 (IL-12) is a heterodimer of interleukin-12 subunit alpha (IL12A, IL-12p35) and interleukin-12 subunit beta (IL12B, IL-12p40). It is a potent immunoregulatory cytokine involved in the generation of cell mediated immunity to intracellular pathogens. It is produced by antigen presenting cells, including dendritic cells, macrophages/monocytes, neutrophils and some B cells (D'Andrea et al. 1992, Kobayashi et al.1989, Heufler et al.1996). It enhances the cytotoxic activity of natural killer (NK) cells and cytotoxic T cells, stimulating proliferation of activated NK and T cells and induces production of interferon gamma (IFN gamma) by these cells (Stern et al. 1990). IL-12 also plays an important role in immunomodulation by promoting cell mediated immunity through induction of a class 1 T helper cell (Th1) immune response. IL-12 may contribute to immunopathological conditions such as rheumatoid arthritis (McIntyre et al. 1996). The receptor for IL-12 is a heterodimer of IL-12Rbeta1 (IL12RB1) and IL-12Rbeta2 (IL12RB2), both highly homologous to Interleukin-6 receptor subunit beta (IL6ST,gp130). Each has an extracellular ligand binding domain, a transmembrane domain and a cytosolic domain containing box 1 and box 2 sequences that mediate binding of Janus family tyrosine kinases (JAKs). IL-12 binding is believed to bring about the heterodimerization and generation of a high affinity receptor complex capable of signal transduction. In this model, receptor dimerization leads to juxtaposition of the cytosolic domains and subsequent tyrosine phosphorylation and activation of JAK2 and TYK2. These activated kinases, in turn, tyrosine phosphorylate and activate several members of the signal transducer and activator of transcription (STAT) family, mainly STAT4, while also STAT1, STAT3 and STAT5 have been reported to be activated (Bacon et al. 1995, Jacobson et al. 1995, Yu et al. 1996, Gollob et al.1995). The STATs translocate to the nucleus to activate transcription of several genes, including IFN gamma. The production of IFN gamma has a pleiotropic effect in the cell, stimulating production of molecules important to cell mediated immunity. In particular, IFN gamma stimulates production of more IL-12 and sets up a positive regulation loop between IL-12 signaling and IFN gamma (Chan et al. 1991). The importance of IL-12 for this loop is demonstrated by IL-12 and STAT4 knockout mice that are severely compromised in IFN-gamma production (Kaplan et al. 1996; Magram et al. 1996), as well as by patients with IL12B mutations that are severely compromised in IFN-gamma production (Altare et al.1998).
Identifier: R-HSA-9020933
Species: Homo sapiens
Interleukin-23 (IL23) is a heterodimer of Interleukin-12 subunit beta (IL12B, IL-12p40), which is shared with IL12, and Interleukin-23 subunit alpha IL23A (IL-23p19) subunit. The functional receptor for IL23 consists of Interleukin-12 receptor subunit beta-1 (IL12RB1), which is shared with the IL12 receptor, and Interleukin-23 receptor (IL23R). IL23R is mainly expresed on activated memory T cells, Natural Killer cells, monocytes/macrophage and at low levels on dendritic cells (DCs). IL23 is mainly secreted by activated macrophages and DCs in peripheral tissues such as skin, intestinal mucosa and lung. IL23 is proinlflammatory and implicated in several autoimmune inflammatory disorders such as colitis, gastritis, psoriasis and arthritis. It is similar to IL-12 both in structure and its ability to memory T cells to increase interferon-γ (IFN-γ) production and proliferation, the ability of IL-23 to induce IL-17. IL23 activates the Janus kinases JAK2 and TYK2, resulting in phosphorylation of the receptor complex, which forms the docking sites for Signal transducer and activator of transcription 3 (STAT3) and STAT4 to bind and become phosphorylated.
Identifier: R-HSA-9020591
Species: Homo sapiens
Interleukin 12 (IL-12) is heterodimeric cytokine produced by dendritic cells, macrophages and neutrophils. It is encoded by the genes Interleukin-12 subunit alpha (IL12A) and Interleukin-12 subunit beta (IL12B), which encode a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40), respectively. The active IL12 heterodimer is sometimes referred to as p70. The p35 component has homology to single-chain cytokines, while p40 is homologous to the extracellular domains of members of the haematopoietic cytokine-receptor family. The IL12 heterodimer therefore resembles a cytokine linked to a soluble receptor. IL12 is involved in the differentiation of naive T cells into Th1 cells and sometimes known as T cell-stimulating factor. IL12 enhances the cytotoxic activity of Natural Killer cells and CD8+ cytotoxic T lymphocytes. IL12 also has anti-angiogenic activity, mediated by increased production of CXCL10 via interferon gamma. The IL12 receptor is a heterodimer formed by Interleukin-12 receptor subunit beta-1 (IL12RB1) and Interleukin-12 receptor subunit beta-2 (IL12RB2), both of which have extensive homology to IL6ST (gp130), the signal transducing receptor subunit of the IL6-like cytokine superfamily. IL-12RB2 is considered to play the key role in IL12 function, in part because its expression on activated T cells is stimulated by cytokines that promote Th1 cell development and inhibited by those that promote Th2 cells development. In addition, IL12 binding leads to IL12RB2 tyrosine phosphorylation, which provides binding sites for the kinases Non-receptor tyrosine-protein kinase TYK2 and Tyrosine-protein kinase JAK2. These activate transcription factor proteins in the Signal transducer and activator of transcription (STAT) family, particularly STAT4.
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