Identifiers
NAME:FADD:RIPK1:TNF:TNFR1*:TRADD:TRAF2
Maps_Modules
MODULE:INPUT_ACTIVATORS
MODULE:IMMUNE_STIMULATION
MODULE:IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
CASCADE:TNF
MACROPHAGE
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 modified 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
MODULE:INPUT_ACTIVATORS
MODULE:IMMUNE_STIMULATION
MODULE:IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
CASCADE:TNF
MACROPHAGE
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 modified 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.
→ 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