Identifiers
NAME:FADD:RIPK1:TNF:TNFR1*:TRADD:TRAF2
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
References
PMID:21133840, PMID:24378531
TNF acts through two transmembrane receptors: TNF receptor 1 (TNFR1), also known as p55 or p60, and TNF receptor 2 (TNFR2), also known as p75 or p80. Macrophages are reported to express both receptors.
PMID:21232017, PMID:21133840, PMID:17301840
cIAP1 and cIAP2 modify RIP1, TRAF2 and
themselves with K63-linked ubiquitin chains. This creates docking sites for the LUBAC complex, an E3 ligase capable of forming linear polyubiquitin chains. The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex, which by help of its IKK2 subunit also interacts
with TRADD-bound TRAF2. In parallel, the TAK1-TAB 2 complex interacts with K63-ubiquitin modi???ed RIP1 by use of the K63-ubiquitin binding TAB 2 subunit. TAK1 become activated and then phosphorylates and activates IKK2 which in turn now phosphorylates IjBa, marking it
for K48-ubiquitination and proteasomal degradation.
PMID:11438547, PMID:24378531
Both TNFR1 and TNFR2 signaling pathways induce classical NFkB activation via IKBa degradation.
Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation.
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
Identifiers
NAME:FADD:RIPK1:TNF:TNFR1*:TRADD:TRAF2
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
References
PMID:21133840, PMID:24378531
TNF acts through two transmembrane receptors: TNF receptor 1 (TNFR1), also known as p55 or p60, and TNF receptor 2 (TNFR2), also known as p75 or p80. Macrophages are reported to express both receptors.
PMID:21232017, PMID:21133840, PMID:17301840
cIAP1 and cIAP2 modify RIP1, TRAF2 and
themselves with K63-linked ubiquitin chains. This creates docking sites for the LUBAC complex, an E3 ligase capable of forming linear polyubiquitin chains. The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex, which by help of its IKK2 subunit also interacts
with TRADD-bound TRAF2. In parallel, the TAK1-TAB 2 complex interacts with K63-ubiquitin modi???ed RIP1 by use of the K63-ubiquitin binding TAB 2 subunit. TAK1 become activated and then phosphorylates and activates IKK2 which in turn now phosphorylates IjBa, marking it
for K48-ubiquitination and proteasomal degradation.
PMID:11438547, PMID:24378531
Both TNFR1 and TNFR2 signaling pathways induce classical NFkB activation via IKBa degradation.
Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation.
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
in_re884( Innate Immunity ):
PMID:14660645, PMID:18264787, PMID:11460167
Activated TAK1 phosphorylates IKK-beta proteins
leading to activation of NF-??B downstream of HMGB1.
PMID:24958845, PMID:24699077
The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex downstream of TNF and upregulates IkBa degradetion.
PMID:11280761
VEGF signaling blocs TNF-?? induced activation of I??B kinase (IKK complex).This decreased IKK activation correlated with the inhibition of I??B?? phosphorylation and degradation of I??B?? and I??B?? in HPCs, and this inhibition is inhdependent or FLT1 and KDR
in_re929( Innate Immunity ):
PMID:16713974
TLR2 activates (induces phosphorylation of) ERKs, JNKs, and p38 rapidly and transiently in control macrophages.
This activation is inhibited by IFNG signaling.
in_re930( Innate Immunity ):
PMID:11875494
IL10-induced p38 phosphorylation.
PMID:20435894
SHIP inhibit MAPKp38 activation and prevent
MKNK1 phosphorylation by inhibiting the p38MAPK
pathway downstream of IL10.
PMID:10925299
IL13 induces p38 MAPK phosphorilation and activation, p38 MAPK participates in arginase activation??downstream of IL13.
PMID:23508573
HMGB1 induces activation (phosphorylation) of p38 via TLR4.
PMID:12811837, PMID:16713974
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
→ FADD:RIPK1|ubi:TNF:TNFR1*:TRADD:TRAF2|ubi@INNATE_IMMUNE_CELL_Membrane
+ TNFR1*@INNATE_IMMUNE_CELL_Membrane + TRADD@INNATE_IMMUNE_CELL_Membrane + TRAF2@INNATE_IMMUNE_CELL_Membrane + RIPK1@INNATE_IMMUNE_CELL_Membrane + FADD@INNATE_IMMUNE_CELL_Membrane → FADD:RIPK1:TNF:TNFR1*:TRADD:TRAF2@INNATE_IMMUNE_CELL_Membrane
+ TAB2@INNATE_IMMUNE_CELL_Cytosol + TAB3@INNATE_IMMUNE_CELL_Cytosol → (MAP3K7:TAB2:TAB3)|active@INNATE_IMMUNE_CELL_Cytosol
→ IKBKG|ubi:IKK_beta_*|pho:MHC_class_I*@INNATE_IMMUNE_CELL_Cytosol
→ JNK*|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ p38*|pho|active@INNATE_IMMUNE_CELL_Cytosol