_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e4
_enti_e2
_enti_e3
_enti_e55
_enti_e53
_enti_e59
_enti_e50
_enti_e54
_enti_e56
_enti_e51
_enti_e52
_enti_e61
_enti_e57
_enti_e58
_enti_e62
_enti_e60
g2_fact_g2
g2_fact_g12
g2_fact_g13
g1_fact_g14
g1_fact_g1
p1_propro_p1
PMID: 16979566, 16979568
It is now clear that all type I IFNs bind to the same dimeric receptor, but different type I IFNs elicit somewhat different biological responses.
PMID: 16979566, 6175095
By the early 1980s, binding studies with radiolabeled IFN proteins had led to the conclusion that there are specific high-affinity cell-surface receptors for IFNs, that different subspecies of type I IFN (IFN-α and IFN-beta) share a common receptor, and that receptors for type I and type II IFN are distinct.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 16979566, 6175095
By the early 1980s, binding studies with radiolabeled IFN proteins had led to the conclusion that there are specific high-affinity cell-surface receptors for IFNs, that different subspecies of type I IFN (IFN-α and IFN-beta) share a common receptor, and that receptors for type I and type II IFN are distinct.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 16979566, 8197455
Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.
c7 cso30:c:InputProcess connector
c11 cso30:c:InputAssociation connector
c8 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 16979566, 8197455
Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.
c9 cso30:c:InputProcess connector
c12 cso30:c:InputAssociation connector
c10 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 16979566, 8197455
Gradual elucidation of the details of the JAK-STAT signaling pathway activated by IFNs helped to clarify not only the molecular mechanisms responsible for IFN actions, but also laid the groundwork for understanding the actions of many other cytokines.
c13 cso30:c:InputAssociation connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 16979566, 17838106
IFN-gamma owes its discovery to the finding that the addition of phytohemagglutinin, a mitogenic lectin, to a suspension of human leucocytes elicited IFN production.
c17 cso30:c:InputAssociation connector
c18 cso30:c:InputAssociation connector
c16 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 16979566, 5233831
Double-stranded RNA from statolon or helenine, and also synthetic double-stranded RNA, poly (I).poly(C), readily triggered IFN production in intact animals or in cell cultures.
c19 cso30:c:InputAssociation connector
c23 cso30:c:InputAssociation connector
c20 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 16979566, 5233831
Double-stranded RNA from statolon or helenine, and also synthetic double-stranded RNA, poly (I).poly(C), readily triggered IFN production in intact animals or in cell cultures.
c21 cso30:c:InputAssociation connector
c22 cso30:c:InputAssociation connector
p9_propro_p9
PMID: 16979566, 4366491, 1067606
Two of the IFN-induced proteins central to IFN's antiviral actions, 2′-5′ oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.
c24 cso30:c:InputProcess connector
c26 cso30:c:InputAssociation connector
c25 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 16979566, 4366491, 1067606
Two of the IFN-induced proteins central to IFN's antiviral actions, 2′-5′ oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.
c27 cso30:c:InputAssociation connector
c29 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 16979566, 4366491, 1067606
Two of the IFN-induced proteins central to IFN's antiviral actions, 2′-5′ oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.
c28 cso30:c:InputAssociation connector
c30 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 16979566, 4366491, 1067606
Two of the IFN-induced proteins central to IFN's antiviral actions, 2′-5′ oligoadenylate synthetase and double-stranded RNA-dependent protein kinase (PKR), were shown to require double-stranded RNA for their activation.
c31 cso30:c:InputProcess connector
c33 cso30:c:InputAssociation connector
c32 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 16979566, 11607032
Molecular pathways mediating cellular responses to double-stranded RNA remained largely unknown until the demonstration that toll-like receptor 3 (TLR3) recognizes double-stranded RNA.
PMID: 16979566, 16979569
As explained in more detail in the accompanying review, this cytosolic pathway is functional mainly in specialized cells, namely dendritic cells (DCs).
c34 cso30:c:InputProcess connector
c36 cso30:c:InputProcess connector
c35 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 16979566, 16625202, 15208624
It is now apparent that the main pathway of type I IFN induction by double-stranded RNA and various RNA-containing viruses, which can be activated in a variety of cell types, is triggered by the cytosolic caspase-recruitment domain (CARD)-containing helicases RIG-I or MDA5.
c37 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 16979566, 16625202, 15208624
It is now apparent that the main pathway of type I IFN induction by double-stranded RNA and various RNA-containing viruses, which can be activated in a variety of cell types, is triggered by the cytosolic caspase-recruitment domain (CARD)-containing helicases RIG-I or MDA5.
c38 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c42 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c46 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c49 cso30:c:InputProcess connector
c50 cso30:c:InputProcess connector
c51 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c52 cso30:c:InputAssociation connector
c58 cso30:c:InputAssociation connector
c55 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c53 cso30:c:InputAssociation connector
c59 cso30:c:InputAssociation connector
c56 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 16979566
In addition to double-stranded RNA, other microbial components or products have been shown to trigger type I IFN production through other pathways, including single-stranded viral RNA (acting on TLR7 and TLR8) and viral or bacterial DNA (via TLR9).
c54 cso30:c:InputAssociation connector
c60 cso30:c:InputAssociation connector
c57 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 16979566, 16410796, 16979569
Although nucleic acids are arguably the most important activators of type I IFN production, bacterial LPS is now known to trigger IFN production in macrophages and DCs via TLR4.
c61 cso30:c:InputProcess connector
c62 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 16979566, 16410796, 16979569
Although nucleic acids are arguably the most important activators of type I IFN production, bacterial LPS is now known to trigger IFN production in macrophages and DCs via TLR4.
c66 cso30:c:InputAssociation connector
c65 cso30:c:InputAssociation connector
c64 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 16979566, 11244049
The earliest-discovered members of this family, IRF-1 and IRF-2, were shown to be important in a variety of innate and adaptive immune responses, including T helper 1 responses and natural killer (NK) cell differentiation.
c67 cso30:c:InputAssociation connector
p25_propro_p25
PMID: 16979566, 11244049
The earliest-discovered members of this family, IRF-1 and IRF-2, were shown to be important in a variety of innate and adaptive immune responses, including T helper 1 responses and natural killer (NK) cell differentiation.
c68 cso30:c:InputAssociation connector
p26_propro_p26
PMID: 16979566, 9707562, 9822609
Two other members of the IRF family, IRF-3 and IRF-7, have been found to play key roles in type I IFN gene activation.
c69 cso30:c:InputAssociation connector
c70 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 16979566, 9707562, 9822609
Two other members of the IRF family, IRF-3 and IRF-7, have been found to play key roles in type I IFN gene activation.
c71 cso30:c:InputAssociation connector
c72 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 16979566, 15665823
For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.
c73 cso30:c:InputProcess connector
c78 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 16979566, 15665823
For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.
c75 cso30:c:InputProcess connector
c77 cso30:c:InputAssociation connector
c76 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 16979566, 15665823
For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.
c82 cso30:c:InputAssociation connector
c79 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 16979566, 15665823
For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.
c83 cso30:c:InputAssociation connector
c80 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 16979566, 15665823
For example, MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of the proinflammatory cytokines TNF-alpha, IL-6, and IL-12, but not for IFN-alpha and IFN-beta induction.
c84 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
IFN Type I_enti_MO000016658
IFN Type I
Type I IFN receptor dimer_enti_e5
Type I IFN receptor dimer
IFN Type I: Type I IFN receptor dimer_enti_e6
IFN Type I: Type I IFN receptor dimer
IFNGR 1: IFNGR 2_enti_e11
IFNGR 1: IFNGR 2
IFN Type II_enti_MO000016664
IFN Type II
IFN Type II: IFNGR 1: IFNGR 2_enti_e12
IFN Type II: IFNGR 1: IFNGR 2
Jak_enti_e13
Jak
Jak{activated}_enti_e14
Jak{activated}
STATs_enti_MO000016656
STATs
STATs{activated}_enti_e15
STATs{activated}
IFNgamma_enti_MO000016665
IFNgamma
IFN-gamma_enti_G010453
IFN-gamma
phytohemagglutinin_enti_e16
phytohemagglutinin
dsRNA_enti_MO000022224
dsRNA
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
IFN_enti_e17
IFN
poly I: C_enti_e18
poly I: C
IFN_enti_e19
IFN
PKR_enti_MO000008179
PKR
PKR{activated}_enti_e20
PKR{activated}
PKR_enti_e21
PKR
OAS_enti_G010199
OAS
OAS_enti_e22
OAS
OAS{activated}_enti_e23
OAS{activated}
TLR3_enti_MO000019398
TLR3
RIG1_enti_e24
RIG1
dsRNA: RIG1 _enti_e25
dsRNA: RIG1
MDA-5_enti_MO000103999
MDA-5
dsRNA: MDA-5_enti_e26
dsRNA: MDA-5
TLR8_enti_MO000042007
TLR8
TLR9_enti_MO000042012
TLR9
TLR7_enti_MO000042126
TLR7
ssRNA_enti_e27
ssRNA
pathogenic DNA_enti_e28
pathogenic DNA
pathogenic DNA: TLR9_enti_e29
pathogenic DNA: TLR9
ssRNA: TLR7_enti_e30
ssRNA: TLR7
ssRNA: TLR8_enti_e31
ssRNA: TLR8
IFN Type I_enti_e32
IFN Type I
IFN Type I_enti_e33
IFN Type I
TLR4_enti_MO000019394
TLR4
LPS_enti_MO000016882
LPS
LPS: TLR4_enti_e34
LPS: TLR4
IRF-1_enti_MO000007685
IRF-1
IRF-2_enti_MO000007690
IRF-2
IRF-3_enti_MO000007694
IRF-3
IRF-7_enti_MO000007702
IRF-7
ligand: TLR_enti_e35
ligand: TLR
IRF-5_enti_MO000007700
IRF-5
IRF-5{activated}_enti_e36
IRF-5{activated}
MyD88_enti_MO000016573
MyD88
MyD88{activated}_enti_e37
MyD88{activated}
TNF-alpha_enti_G010329
TNF-alpha
IL-6_enti_G010262
IL-6
IL-12 p40_enti_G010657
IL-12 p40