_enti_e7
_enti_e8
_enti_e5
_enti_e9
_enti_e1
_enti_e10
_enti_e3
_enti_e4
_enti_e2
_enti_e55
_enti_e59
_enti_e53
_enti_e51
_enti_e50
_enti_e56
_enti_e52
_enti_e54
_enti_e57
_enti_e61
_enti_e58
_enti_e62
_enti_e60
g2_fact_g2
g2_fact_g12
g2_fact_g13
g1_fact_g1
g1_fact_g14
p1_propro_p1
PMID: 15331118
Activation of T cells is initiated by engagement of the T cell receptor (TCR) with peptide antigen presented by the major histocompatibility complex (MHC) on antigen-presenting cells (APC).
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
c4 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 15331118
Activation of T cells is initiated by engagement of the T cell receptor (TCR) with peptide antigen presented by the major histocompatibility complex (MHC) on antigen-presenting cells (APC) or anti-receptor antibodies.
c5 cso30:c:InputProcess connector
c6 cso30:c:InputProcess connector
c7 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck.
c8 cso30:c:InputProcess connector
c11 cso30:c:InputAssociation connector
c9 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck.
c12 cso30:c:InputProcess connector
c15 cso30:c:InputAssociation connector
c13 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck, which mediate the phosphorylation of immunoreceptor tyrosine-based activation motifs on CD3-ζ.
c16 cso30:c:InputProcess connector
c18 cso30:c:InputAssociation connector
c17 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck, which mediate the phosphorylation of immunoreceptor tyrosine-based activation motifs on CD3-ζ.
c19 cso30:c:InputAssociation connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck, which mediate the phosphorylation of immunoreceptor tyrosine-based activation motifs on CD3-ζ. This leads to the recruitment and activation of ZAP-70.
c23 cso30:c:InputProcess connector
c141 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p10_propro_p10
PMID:15331118
ZAP-70 subsequently phosphorylates adaptor proteins, such as the linker for activated T cells (LAT), which in turn mobilize other adaptor proteins or enzymes to amplify and to transmit signals downstream through different stages and ultimately lead to the activation of different nuclear transcription factors necessary for cytokine gene transcription.
c33 cso30:c:InputAssociation connector
c31 cso30:c:InputProcess connector
c28 cso30:c:OutputProcess connector
p11_propro_p11
PMID:15331118
LAT in turn mobilize other adaptor proteins or enzymes to amplify and to transmit signals downstream through different stages and ultimately lead to the activation of different nuclear transcription factors necessary for cytokine gene transcription.
c37 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p12_propro_p12
PMID:15331118
LAT in turn mobilize other adaptor proteins or enzymes to amplify and to transmit signals downstream through different stages and ultimately lead to the activation of different nuclear transcription factors necessary for cytokine gene transcription.
c127 cso30:c:InputProcess connector
c35 cso30:c:InputAssociation connector
c36 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 15331118
The binding of LPS to its receptor CD14 at cell surface triggers its association with transmembrane protein toll-like receptor (TLR), mainly TLR2 and TLR4.
c38 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 15331118
The binding of LPS to its receptor CD14 at cell surface triggers its association with transmembrane protein toll-like receptor (TLR), mainly TLR2 and TLR4.
c41 cso30:c:InputProcess connector
c42 cso30:c:InputProcess connector
c43 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 15331118
The binding of LPS to its receptor CD14 at cell surface triggers its association with transmembrane protein toll-like receptor (TLR), mainly TLR2 and TLR4.
c44 cso30:c:InputProcess connector
c45 cso30:c:InputProcess connector
c128 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK.
c46 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK.
c49 cso30:c:InputProcess connector
c50 cso30:c:InputProcess connector
c51 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK.
c52 cso30:c:InputProcess connector
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK.
c55 cso30:c:InputProcess connector
c56 cso30:c:InputProcess connector
c57 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK which leads to IRAK activation.
c58 cso30:c:InputProcess connector
c59 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 15331118
TRAF6 is phosphorylated and recruited to IRAK.
c60 cso30:c:InputProcess connector
c62 cso30:c:InputAssociation connector
c61 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 15331118
TRAF6 is phosphorylated and recruited to IRAK.
c63 cso30:c:InputProcess connector
c64 cso30:c:InputProcess connector
c65 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 15331118
MyD88, a cytoplasmic adaptor protein, responds to CD14/TLR stimulation by recruiting IRAK which leads to IRAK activation.
c66 cso30:c:InputProcess connector
c67 cso30:c:OutputProcess connector
p24_propro_p24
c68 cso30:c:InputProcess connector
c70 cso30:c:InputAssociation connector
c69 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 15331118
TRAF6 is phosphorylated and recruited to IRAK.
c71 cso30:c:InputProcess connector
c72 cso30:c:InputProcess connector
c73 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 15331118
Several tentative molecules have been suggested to relay the signal to IKK complex downstream of TRAF6. NF-κB-inducing kinase (NIK) is one of these molecules.
c74 cso30:c:InputProcess connector
c78 cso30:c:InputAssociation connector
c75 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 15331118
IKK is a major kinase responsible for the phosphorylation of IκB.
c80 cso30:c:InputProcess connector
c82 cso30:c:InputAssociation connector
c81 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 15331118
Phosphorylated IκB is eventually degraded, leaving the NF-κB dimer free and translocate to nucleus
c83 cso30:c:InputProcess connector
c84 cso30:c:OutputProcess connector
c85 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 15331118
Phosphorylated IκB is eventually degraded, leaving the NF-κB dimer free and translocate to nucleus
c86 cso30:c:InputProcess connector
c87 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 15331118
NF-κB binds to the promoter region of COX-2 gene
c88 cso30:c:InputProcess connector
c89 cso30:c:InputProcess connector
c90 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 15331118
Several tentative molecules have been suggested to relay the signal to IKK complex downstream of TRAF6. NF-κB-inducing kinase (NIK) is one of these molecules.
c76 cso30:c:InputProcess connector
c79 cso30:c:InputAssociation connector
c77 cso30:c:OutputProcess connector
p32_propro_p32
PMID: 15331118
Several tentative molecules have been suggested to relay the signal to IKK complex downstream of TRAF6. NF-κB-inducing kinase (NIK) is one of these molecules.
c91 cso30:c:InputProcess connector
c93 cso30:c:InputAssociation connector
c92 cso30:c:OutputProcess connector
p33_propro_p33
PMID: 15331118
NF-κB binds to the promoter region of COX-2 gene and initiates the transcription.
c94 cso30:c:InputProcess connector
c95 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 15331118
The resulting mRNA of COX-2 encodes synthesis of COX-2 enzyme.
c96 cso30:c:InputAssociation connector
c97 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 15331118
COX-2 catalyzes metabolism of AA to PGH2 which is further isomerized to PGE2.
c98 cso30:c:InputAssociation connector
c99 cso30:c:InputProcess connector
c100 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 15331118
COX-2 catalyzes metabolism of AA to PGH2 which is further isomerized to PGE2
c101 cso30:c:InputProcess connector
c102 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 15331118
Ceramide is a sphingolipid second messenger generated from the hydrolysis of membrane sphingomyelin under the action of sphingomyelinase (SMase).
c103 cso30:c:InputProcess connector
c105 cso30:c:InputAssociation connector
c104 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c106 cso30:c:InputProcess connector
c109 cso30:c:InputAssociation connector
c107 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c110 cso30:c:InputAssociation connector
c111 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c112 cso30:c:InputProcess connector
c116 cso30:c:InputAssociation connector
c113 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c114 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c118 cso30:c:InputProcess connector
c120 cso30:c:InputAssociation connector
c119 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c122 cso30:c:InputAssociation connector
c123 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 15331118
ceramide stimulates by itself and also potentiates LPS-induced PGE2 production and COX-2 expression.
c124 cso30:c:InputAssociation connector
c125 cso30:c:OutputProcess connector
p28_propro_p45
PMID: 15331118
Ceramide alone was a weak inducer of NF-κB activation.
c129 cso30:c:InputProcess connector
c131 cso30:c:InputAssociation connector
c130 cso30:c:OutputProcess connector
p42_propro_p46
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c126 cso30:c:InputProcess connector
c133 cso30:c:InputAssociation connector
c132 cso30:c:OutputProcess connector
p38_propro_p47
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c121 cso30:c:InputProcess connector
c135 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p40_propro_p48
PMID: 15331118
Mitogen-activated protein kinase (MAPK) intermediates such as extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinases (JNK), and p38 are involved in LPS- as well as ceramide-induced COX-2 gene expression.
c108 cso30:c:InputProcess connector
c137 cso30:c:InputAssociation connector
c136 cso30:c:OutputProcess connector
p3_propro_p49
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck.
c117 cso30:c:InputProcess connector
c139 cso30:c:InputAssociation connector
c138 cso30:c:OutputProcess connector
p3_propro_p50
PMID: 15331118
Occupancy of the TCR triggers activation of Src family protein tyrosine kinases Fyn and Lck.
c10 cso30:c:InputAssociation connector
c14 cso30:c:InputProcess connector
c140 cso30:c:OutputProcess connector
antigen:MHC_enti_e6
antigen:MHC
TCR_enti_e11
TCR
MHC_enti_e12
MHC
antigen:TCR_enti_e13
antigen:TCR
anti-TCR antibody_enti_e14
anti-TCR antibody
antibody:TCR_enti_e15
antibody:TCR
FYN_enti_e16
FYN
FYN{active}_enti_e17
FYN{active}
LCK_enti_e18
LCK
LCK{active}_enti_e19
LCK{active}
CD3zeta_enti_e20
CD3zeta
CD3zeta{p}_enti_e21
CD3zeta{p}
ZAP70_enti_e22
ZAP70
CD3zeta{p}:ZAP70_enti_e23
CD3zeta{p}:ZAP70
LAT_enti_e25
LAT
LAT{p}_enti_e26
LAT{p}
cytokine genes_enti_e27
cytokine genes
Unknown protein{active}_enti_e28
Unknown protein{active}
CD14_enti_e29
CD14
LPS_enti_e30
LPS
LPS:CD14_enti_e31
LPS:CD14
TLR4_enti_e33
TLR4
LPS:CD14:TLR4_enti_e34
LPS:CD14:TLR4
TLR2_enti_e35
TLR2
LPS:CD14:TLR2_enti_e36
LPS:CD14:TLR2
MYD88_enti_e37
MYD88
LPS:CD14:TLR4:MYD88_enti_e32
LPS:CD14:TLR4:MYD88
LPS:CD14:TLR2:MYD88_enti_e38
LPS:CD14:TLR2:MYD88
IRAK_enti_e39
IRAK
LPS:CD14:TLR4:MYD88:IRAK_enti_e40
LPS:CD14:TLR4:MYD88:IRAK
LPS:CD14:TLR2:MYD88:IRAK_enti_e41
LPS:CD14:TLR2:MYD88:IRAK
LPS:CD14:TLR4:MYD88:IRAK{active}_enti_e42
LPS:CD14:TLR4:MYD88:IRAK{active}
TRAF6_enti_e43
TRAF6
TRAF6{p}_enti_e44
TRAF6{p}
LPS:CD14:TLR4:MYD88:IRAK{active}:TRAF6{p}_enti_e45
LPS:CD14:TLR4:MYD88:IRAK{active}:TRAF6{p}
LPS:CD14:TLR2:MYD88:IRAK{active}_enti_e46
LPS:CD14:TLR2:MYD88:IRAK{active}
LPS:CD14:TLR2:MYD88:IRAK{active}:TRAF6{p}_enti_e47
LPS:CD14:TLR2:MYD88:IRAK{active}:TRAF6{p}
IKKalpha:IKK-beta:IKK-gamma_enti_e48
IKKalpha:IKK-beta:IKK-gamma
IKK-alpha:IKK-beta:IKK-gamma{active}_enti_e49
IKK-alpha:IKK-beta:IKK-gamma{active}
Ikappa-B:NF-kappaB_enti_e63
Ikappa-B:NF-kappaB
IkappaB{p}:NF-kappaB_enti_e64
IkappaB{p}:NF-kappaB
protein remnants_enti_e65
p50:p65_enti_e66
p50:p65
p50:p65_enti_e67
p50:p65
COX2_enti_e68
COX2
COX2:p50:p65_enti_e69
COX2:p50:p65
NIK_enti_e70
NIK
NIK{active}_enti_e71
NIK{active}
COX2_enti_e72
COX2
COX2_enti_e73
COX2
Arachidonic acid_enti_e74
Arachidonic acid
PGH2_enti_e75
PGH2
PGE2_enti_e76
PGE2
Sphingolipid_enti_e77
Sphingolipid
ceramide_enti_e78
ceramide
SMase_enti_e79
SMase
ERK_enti_e80
ERK
ERK{active}_enti_e81
ERK{active}
JNK_enti_e82
JNK
JNK{active}_enti_e83
JNK{active}
p38_enti_e84
p38
p38{active}_enti_e85
p38{active}
Unknown protein_enti_e86
Unknown protein