_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e3
_enti_e4
_enti_e2
_enti_e55
_enti_e59
_enti_e53
_enti_e56
_enti_e51
_enti_e54
_enti_e50
_enti_e52
_enti_e58
_enti_e57
_enti_e61
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
p1_propro_p1
PMID: 18400190
Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.
c4 cso30:c:InputProcess connector
c5 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 18400190
Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.
c6 cso30:c:InputProcess connector
c7 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18400190
Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 18400190
This event provides a docking site for proteins with Src homology 2 domains, one important class of which is the Stat family of transcription factors.
c8 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 18400190, 14668806
With seven members in all (Stat1, Stat2, Stat3, Stat4, Stat5a, Stat5b, and Stat6), these DNA-binding proteins provide a rapid membrane to nucleus mechanism for regulation of gene expression.
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 18400190, 14668806
With seven members in all (Stat1, Stat2, Stat3, Stat4, Stat5a, Stat5b, and Stat6), these DNA-binding proteins provide a rapid membrane to nucleus mechanism for regulation of gene expression.
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 18400190
As an example of the overall importance of cytokine-cytokine receptor-Jak-Stat pathway signaling in thymic T cell development, IL-7 signaling ensures development of appropriate lymphocyte numbers.
PMID: 18400190
Stat5 signaling from cytokines that use γc is essential for T cell development.
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 18400190
Stat5 signaling from cytokines that use γc is essential for T cell development.
PMID: 18400190
Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).
c21 cso30:c:InputAssociation connector
c19 cso30:c:InputProcess connector
c148 cso30:c:InputInhibitor connector
c20 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 18400190, 16418296
IL-7 activates Stat5a and Stat5b, and deletion of the locus encoding Stat5a and Stat5b also results in a severe SCID phenotype.
PMID: 18400190
Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).
c22 cso30:c:InputProcess connector
c26 cso30:c:InputAssociation connector
c149 cso30:c:InputInhibitor connector
c23 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 18400190, 16418296
IL-7 activates Stat5a and Stat5b, and deletion of the locus encoding Stat5a and Stat5b also results in a severe SCID phenotype.
PMID: 18400190
Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).
c24 cso30:c:InputProcess connector
c27 cso30:c:InputAssociation connector
c150 cso30:c:InputInhibitor connector
c25 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 18400190
Stat5 signaling from cytokines that use γc is essential for T cell development.
PMID: 18400190, 16455959
Deficiency of gamma-c or Jak3 causes a failure to produce Foxp3-positive regulatory T cells.
PMID: 18400190
On one hand, Socs1 regulates T cell development by inhibiting gamma-c signaling.
c28 cso30:c:InputAssociation connector
c49 cso30:c:InputAssociation connector
c172 cso30:c:InputInhibitor connector
p12_propro_p12
PMID: 18400190
Stat5 signaling controls the development of FoxP3-positive Treg cells in part through the direct activation of Foxp3 gene expression.
PMID: 18400190
Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.
c46 cso30:c:InputAssociation connector
c30 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 18400190
IL-12 activates Stat4, whereas IL-4 activates Stat6.
c31 cso30:c:InputProcess connector
c35 cso30:c:InputAssociation connector
c32 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 18400190
IL-12 activates Stat4, whereas IL-4 activates Stat6.
c33 cso30:c:InputProcess connector
c36 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 18400190
These fates are driven by the cytokine milieu with IL-12 driving Th1 cell differentiation and IL-4 promoting Th2 cell differentiation.
PMID: 18400190, 11121747
Stat4- and Stat6-deficient mice have impaired Th1 and Th2 cell responses, respectively.
PMID: 18400190, 12242445
Depending upon the circumstance, type I IFN signaling may enhance or inhibit Th1 cell responses.
c37 cso30:c:InputAssociation connector
p16_propro_p16
PMID: 18400190
These fates are driven by the cytokine milieu with IL-12 driving Th1 cell differentiation and IL-4 promoting Th2 cell differentiation.
PMID: 18400190, 11121747
Stat4- and Stat6-deficient mice have impaired Th1 and Th2 cell responses, respectively.
c38 cso30:c:InputAssociation connector
p17_propro_p17
PMID: 18400190
In this regard, it is important to note that type I IFNs also activate Stat4.
c39 cso30:c:InputProcess connector
c41 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 18400190
Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.
c29 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 18400190
Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 18400190, 17227828
Accordingly, deficiency of both Stat5a and Stat5b also leads to loss of Treg cells and inability to induce Treg cells in vitro.
PMID: 18400190
In both cases, cytokines that use gamma-c are important drivers of Treg cell development.
c47 cso30:c:InputAssociation connector
c48 cso30:c:InputAssociation connector
p21_propro_p21
PMID: 18400190, 17581589, 17581537
Th17 cells can be generated from naive CD4+ T cells by IL-6 and TGF-beta but can also produce another cytokine IL-21, which promotes IL-17 production in an autocrine-paracrine manner.
c60 cso30:c:InputAssociation connector
c61 cso30:c:InputAssociation connector
c152 cso30:c:InputInhibitor connector
c51 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 18400190
IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 18400190
IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.
c132 cso30:c:InputProcess connector
c133 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 18400190
IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.
c55 cso30:c:InputProcess connector
c59 cso30:c:InputAssociation connector
c151 cso30:c:InputInhibitor connector
c56 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c64 cso30:c:InputProcess connector
c68 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c65 cso30:c:InputProcess connector
c69 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c62 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c70 cso30:c:InputAssociation connector
c71 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c73 cso30:c:InputAssociation connector
c72 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 18400190, 18164222
Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated.
PMID: 18400190
IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression.
c74 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 18400190, 18164222
Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated.
PMID: 18400190
IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression.
c75 cso30:c:InputAssociation connector
c77 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 18400190, 18164222
Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated.
PMID: 18400190
IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression.
PMID: 18400190, 17363300
Parenthetically, it is interesting to note that IL-2 acting through Stat5 inhibits Th17 cell differentiation.
c78 cso30:c:InputAssociation connector
c79 cso30:c:InputAssociation connector
c83 cso30:c:InputInhibitor connector
p33_propro_p33
PMID: 18400190, 17363300
Parenthetically, it is interesting to note that IL-2 acting through Stat5 inhibits Th17 cell differentiation.
c80 cso30:c:InputProcess connector
c82 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 18400190
whereas IL-6 and TGF-beta-1 are important for the differentiation of Th17 cells, IL-6 alone so far appears to be capable of inducing IL-22.
c84 cso30:c:InputAssociation connector
c85 cso30:c:InputAssociation connector
p35_propro_p35
PMID: 18400190
whereas IL-6 and TGF-beta-1 are important for the differentiation of Th17 cells, IL-6 alone so far appears to be capable of inducing IL-22.
c86 cso30:c:InputAssociation connector
c87 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 18400190
An additional complexity of Th17 T cells in inflammation concerns the Stat3-activating cytokine IL-22.
c88 cso30:c:InputProcess connector
c90 cso30:c:InputAssociation connector
c89 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 18400190
Importantly, the genes encoding the Socs proteins are direct targets of Stat proteins; the Jak-Stat cascades thereby control their own signaling output by feedback inhibition.
c92 cso30:c:InputAssociation connector
c91 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 18400190, 12076535, 10051596
Each of the eight Socs proteins have two major domains, an SH2 domain and a Socs box that complexes with elongins B and C, a cullin and Rbx2, to form a E3 ubiquitin ligase.
c93 cso30:c:InputProcess connector
c94 cso30:c:InputProcess connector
c95 cso30:c:InputProcess connector
c96 cso30:c:InputProcess connector
c98 cso30:c:InputProcess connector
c97 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 18400190
The Socs SH2 domains bind phosphorylated tyrosine residues in their substrates. The best characterized Socs substrates are specific tyrosine residues in the cytoplasmic tails of cytokine receptors.
c99 cso30:c:InputProcess connector
c100 cso30:c:InputProcess connector
c101 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 18400190
The current model of Socs function postulates that the E3 activity of a Socs protein will target the substrate to be ubiquitinated and then directed to the proteosome for degradation.
c102 cso30:c:InputProcess connector
c103 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 18400190
The current model of Socs function postulates that the E3 activity of a Socs protein will target the substrate to be ubiquitinated and then directed to the proteosome for degradation.
c104 cso30:c:InputProcess connector
c105 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 18400190
The G-CSFR is responsible for transducing the signals from G-CSF via four tyrosine residues located in the cytoplasmic tail of the receptor.
c106 cso30:c:InputProcess connector
c107 cso30:c:InputProcess connector
c108 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 18400190
G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases.
c109 cso30:c:InputProcess connector
c111 cso30:c:InputAssociation connector
c110 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 18400190
G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases.
PMID: 18400190, 12133942
Indeed, Socs3 binds to one of the tyrosine residues in the G-CSFR (Y729) and restricts the amplitude of Stat3 signaling.
c112 cso30:c:InputProcess connector
c114 cso30:c:InputAssociation connector
c121 cso30:c:InputInhibitor connector
c113 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 18400190
G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases.
c115 cso30:c:InputAssociation connector
c116 cso30:c:InputProcess connector
c117 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 18400190, 12133942
Indeed, Socs3 binds to one of the tyrosine residues in the G-CSFR (Y729) and restricts the amplitude of Stat3 signaling.
c118 cso30:c:InputProcess connector
c119 cso30:c:InputProcess connector
c120 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 18400190
Thus, loss of Socs3 causes increased G-CSFR signaling leading to increased neutrophil numbers, whereas loss of Stat3 (and failure to induce Socs3 expression) also leads to increased neutrophil numbers.
c122 cso30:c:InputAssociation connector
p48_propro_p48
PMID: 18400190
Thus, loss of Socs3 causes increased G-CSFR signaling leading to increased neutrophil numbers, whereas loss of Stat3 (and failure to induce Socs3 expression) also leads to increased neutrophil numbers.
PMID: 18400190
Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (“anti-inflammatory response” AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.
c124 cso30:c:InputAssociation connector
c123 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 18400190
Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (“anti-inflammatory response” AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.
c126 cso30:c:InputProcess connector
c139 cso30:c:InputAssociation connector
c127 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 18400190
Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (“anti-inflammatory response” AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.
c129 cso30:c:InputAssociation connector
c125 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 18400190
Gp130 has multiple tyrosine residues in its cytoplasmic tail, all of which bar one, Y757, serve as docking sites for Stat proteins (especially Stat3)
PMID: 18400190
Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).
c50 cso30:c:InputProcess connector
c57 cso30:c:InputProcess connector
c146 cso30:c:InputInhibitor connector
c52 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 18400190
Gp130 has multiple tyrosine residues in its cytoplasmic tail, all of which bar one, Y757, serve as docking sites for Stat proteins (especially Stat3)
PMID: 18400190
Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).
c58 cso30:c:InputProcess connector
c130 cso30:c:InputProcess connector
c147 cso30:c:InputInhibitor connector
c131 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c134 cso30:c:InputProcess connector
c135 cso30:c:OutputProcess connector
c136 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 18400190, 16698929, 17884812
However, Stat3 also directly regulates the expression of Il21 and Il17.
c137 cso30:c:InputProcess connector
c138 cso30:c:OutputProcess connector
c128 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 18400190, 16678769, 12687404
Y757 docks the SH2 domain of Socs3 and is by far the best-characterized Socs-cytokine receptor interaction.
c140 cso30:c:InputProcess connector
c144 cso30:c:InputProcess connector
c142 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 18400190, 16678769, 12687404
Y757 docks the SH2 domain of Socs3 and is by far the best-characterized Socs-cytokine receptor interaction.
c141 cso30:c:InputProcess connector
c145 cso30:c:InputProcess connector
c143 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 18400190, 18276893
IL-22 induces the expression of antimicrobial proteins, including S1008A, a zinc and manganese chelating protein that deprives bacteria of essential cations.
c154 cso30:c:InputAssociation connector
c153 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 18400190
Socs1, unlike the broad expression of Socs3, is activated predominantly by interferon signaling, although other cytokines such as IL-4 also activate Socs1 expression but in a cell-type-dependent way.
c156 cso30:c:InputAssociation connector
c155 cso30:c:OutputProcess connector
p59_propro_p59
PMID: 18400190
Because TLR signaling induces autocrine-paracrine IFN-alpha-beta production, this might underlie the cause of LPS sensitivity in Socs1/; Ifng/ mice.
c158 cso30:c:InputAssociation connector
c159 cso30:c:InputAssociation connector
c157 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 18400190
Because TLR signaling induces autocrine-paracrine IFN-alpha-beta production, this might underlie the cause of LPS sensitivity in Socs1/; Ifng/ mice.
c161 cso30:c:InputAssociation connector
c162 cso30:c:InputAssociation connector
c160 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 18400190, 16415872
Mansell et al. have demonstrated that Socs1 can bind to and regulate the degradation of Mal (also known as TIRAP), an adaptor molecule specifically associated with TLR2 and TLR4 signaling.
c166 cso30:c:InputProcess connector
c167 cso30:c:InputProcess connector
c168 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 18400190, 16439361
Previous studies had shown that the tyrosine kinase Btk phosphorylates Mal, providing binding sites for Socs1.
c163 cso30:c:InputAssociation connector
c164 cso30:c:InputProcess connector
c165 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 18400190, 16415872
Mansell et al. have demonstrated that Socs1 can bind to and regulate the degradation of Mal (also known as TIRAP), an adaptor molecule specifically associated with TLR2 and TLR4 signaling.
c169 cso30:c:InputProcess connector
c170 cso30:c:OutputProcess connector
c171 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 18400190
The chemokine CXCL12 activates CXCR4 and induces phosphorylation of FAK, a ubiquitous tyrosine kinase, in addition to other pathways.
PMID: 18400190, 12163560
Therefore, the assignment of FAK as a substrate of Socs3 potentially explains previous data that suggested that Socs3 directly regulates CXCR4 to inhibit its activity.
c173 cso30:c:InputProcess connector
c175 cso30:c:InputAssociation connector
c179 cso30:c:InputInhibitor connector
c174 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 18400190
The chemokine CXCL12 activates CXCR4 and induces phosphorylation of FAK, a ubiquitous tyrosine kinase, in addition to other pathways.
PMID: 18400190
Le et al. have shown that Socs3 is crucial to regulate the amounts of CXCL12-activated phospho-FAK because Socs3-deficient B cells have increased amount of phospho-FAK.
c176 cso30:c:InputProcess connector
c178 cso30:c:InputAssociation connector
c182 cso30:c:InputInhibitor connector
c177 cso30:c:OutputProcess connector
p66_propro_p66
PMID: 18400190, 12387736
Link and colleagues have also postulated that signals from the G-CSFR negatively regulate CXCL12 amounts in the bone marrow, thereby allowing escape of neutrophils into the circulation.
c180 cso30:c:InputInhibitor connector
c181 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 18400190
Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.
c183 cso30:c:InputAssociation connector
c184 cso30:c:InputProcess connector
c185 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 18400190
Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.
c189 cso30:c:InputAssociation connector
c194 cso30:c:InputAssociation connector
c187 cso30:c:OutputProcess connector
p69_propro_p69
PMID: 18400190
Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.
c186 cso30:c:InputAssociation connector
c190 cso30:c:InputAssociation connector
c188 cso30:c:OutputProcess connector
p70_propro_p70
PMID: 18400190
Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.
c191 cso30:c:InputProcess connector
c193 cso30:c:InputAssociation connector
c192 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 18400190, 18400189
Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).
c195 cso30:c:InputProcess connector
c197 cso30:c:InputAssociation connector
c196 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 18400190, 18400189
Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).
c199 cso30:c:InputAssociation connector
c205 cso30:c:InputAssociation connector
c198 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 18400190, 18400189
Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).
c200 cso30:c:InputProcess connector
c204 cso30:c:InputAssociation connector
c201 cso30:c:OutputProcess connector
p74_propro_p74
PMID: 18400190, 18400189
Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).
c203 cso30:c:InputAssociation connector
c202 cso30:c:OutputProcess connector
cytokines_enti_MO000019387
cytokines
cytokine receptor: Jak1: Jak2_enti_e5
cytokine receptor: Jak1: Jak2
cytokine: cytokine receptor: Jak1: Jak2_enti_e6
cytokine: cytokine receptor: Jak1: Jak2
Jak3_enti_MO000000147
Jak3
cytokine: cytokine receptor: Jak1: Jak2_enti_e11
cytokine: cytokine receptor: Jak1: Jak2
cytokine: cytokine receptor {pY}: Jak1: Jak2_enti_e12
cytokine: cytokine receptor {pY}: Jak1: Jak2
cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs_enti_e13
cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs
STATs_enti_MO000016656
STATs
STATs {nuclear}_enti_e14
STATs {nuclear}
STATs {nuclear}: DNA_enti_e15
STATs {nuclear}: DNA
DNA_enti_e16
DNA
IL-7_enti_MO000016830
IL-7
SOCS-1_enti_MO000017004
SOCS-1
IL-7R: gamma-c_enti_e17
IL-7R: gamma-c
IL-7: IL-7R: gamma-c_enti_e18
IL-7: IL-7R: gamma-c
IL-6: IL-6R: gp130_enti_e19
IL-6: IL-6R: gp130
STAT5A_enti_MO000013126
STAT5A
STAT5B_enti_MO000013133
STAT5B
STAT5_enti_MO000016876
STAT5
STAT5{activated}_enti_e20
STAT5{activated}
STAT5A {activated}_enti_e21
STAT5A {activated}
STAT5B {activated}_enti_e22
STAT5B {activated}
FOXP3_enti_G011587
FOXP3
IL-12_enti_MO000017265
IL-12
IL-4_enti_MO000017053
IL-4
STAT4_enti_MO000017181
STAT4
STAT4 {activated}_enti_e23
STAT4 {activated}
STAT6_enti_MO000013130
STAT6
STAT6 {activated}_enti_e24
STAT6 {activated}
IFN Type I_enti_MO000016658
IFN Type I
STAT5{nuclear}}_enti_e25
STAT5{nuclear}}
FOXP3 gene_enti_e26
FOXP3 gene
STAT5{nuclear}: FOXP3 gene_enti_e27
STAT5{nuclear}: FOXP3 gene
STAT3_enti_MO000013122
STAT3
STAT3 {activated}_enti_e28
STAT3 {activated}
IL-17_enti_MO000007327
IL-17
IL17_enti_G011341
IL17
IL23: IL23R: gp130_enti_e29
IL23: IL23R: gp130
IL21_enti_G011174
IL21
IL-21: IL-21R:gamma-c_enti_e30
IL-21: IL-21R:gamma-c
STAT3 {nuclear}_enti_e31
STAT3 {nuclear}
IL21 gene_enti_e32
IL21 gene
IL17gene_enti_e33
IL17gene
STAT3 {nuclear}: IL21gene_enti_e34
STAT3 {nuclear}: IL21gene
STAT3 {nuclear}: IL17gene_enti_e35
STAT3 {nuclear}: IL17gene
RORA_enti_G011523
Indirect
RORA
RORC_enti_e36
RORC
IL-2_enti_MO000017061
IL-2
TGFbeta1_enti_MO000017443
TGFbeta1
IL22_enti_G011175
IL22
IL-22_enti_MO000019517
IL-22
SOCS_enti_e37
SOCS
elongin B_enti_MO000018947
elongin B
elongin C_enti_MO000018946
elongin C
culin_enti_e38
culin
Rbx2_enti_e39
Rbx2
E3 ubiquitin ligase_enti_e40
E3 ubiquitin ligase
SOCS_enti_e41
SOCS
cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs: E3 ubiquitin ligase_enti_e42
cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs: E3 ubiquitin ligase
cytokine: cytokine receptor {pY} {ub}: Jak1: Jak2: STATs: E3 ubiquitin ligase_enti_e43
cytokine: cytokine receptor {pY} {ub}: Jak1: Jak2: STATs: E3 ubiquitin ligase
protein remnants_enti_MO000019479
protein remnants
GCSFR_enti_MO000089770
GCSFR
G-CSF_enti_MO000003473
G-CSF
G-CSF: GCSFR_enti_e44
G-CSF: GCSFR
MAPK_enti_MO000016894
MAPK
MAPK {activated}_enti_e45
MAPK {activated}
SOCS-3_enti_MO000017121
SOCS-3
G-CSF: GCSFR: SOCS-3_enti_e46
G-CSF: GCSFR: SOCS-3
SOCS3_enti_G011948
SOCS3
AIR_enti_e47
AIR
IL-6: IL-6R: gp130: STAT3_enti_e48
IL-6: IL-6R: gp130: STAT3
IL-6: IL-6R: gp130: STAT3_enti_e49
IL-6: IL-6R: gp130: STAT3
IL23: IL23R: gp130: STAT3_enti_e63
IL23: IL23R: gp130: STAT3
IL23: IL23R: gp130: STAT3{activated}_enti_e64
IL23: IL23R: gp130: STAT3{activated}
IL-6: IL-6R: gp130: SOCS3_enti_e65
IL-6: IL-6R: gp130: SOCS3
IL23: IL23R: gp130: SOCS3_enti_e66
IL23: IL23R: gp130: SOCS3
IL-10: IL-10R_enti_e67
IL-10: IL-10R
S1008A_enti_e68
S1008A
SOCS1_enti_G010539
SOCS1
TLR ligand: TLR_enti_e69
TLR ligand: TLR
IFN-alpha_enti_G016992
IFN-alpha
IFNalpha_enti_MO000016659
IFNalpha
IFNbeta_enti_MO000016660
IFNbeta
IFN-beta_enti_G010228
IFN-beta
Btk_enti_MO000001935
Btk
MAL_enti_MO000068831
MAL
MAL {p}_enti_e70
MAL {p}
MAL{p}: SOSC-1_enti_e71
MAL{p}: SOSC-1
CXCL12_enti_MO000019001
CXCL12
CXCR4_enti_MO000017157
CXCR4
CXCR4 {activated}_enti_e72
CXCR4 {activated}
FAK family_enti_MO000016855
FAK family
FAK {p}_enti_e73
FAK {p}
p38_enti_MO000000022
p38
p38 {activated}_enti_e74
p38 {activated}
ERK_enti_MO000000011
ERK
IL-10_enti_MO000017247
IL-10
zymosan_enti_e75
zymosan
IL10_enti_G011345
IL10
ERK {activated}_enti_e76
ERK {activated}
IL27_enti_MO000062893
IL27
STAT1_enti_MO000013119
STAT1
STAT1 {activated}_enti_e77
STAT1 {activated}