Identifiers
HUGO:MAP3K7
Maps_Modules
MACROPHAGE
MODULE:CORE_SIGNALING_PATHWAYS
MODULE:IMMUNOSTIMULATORY_CORE_PATHWAYS
CASCADE:TLR2_4
CASCADE:TNF
References
PMID:14660645, PMID:18264787, PMID:12620219
IRAK-1 interacts with the downstream adaptor TRAF6,
resulting in formation of a complex that also includes TAK1 and TAB2.
IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol,
where they form a multiprotein complex with other cytosolic proteins,
which are needed for stimulation of TAK1 kinase activity.
PMID:21232017, PMID:21133840 PMID:17301840, PMID:18641653, PMID:24958845, PMID:16603398, PMID:14633987
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 modieed 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
+ TAB2@INNATE_IMMUNE_CELL_Cytosol + TAB3@INNATE_IMMUNE_CELL_Cytosol → (MAP3K7:TAB2:TAB3)|active@INNATE_IMMUNE_CELL_Cytosol
→ IKK_alpha_*|pho|hm2|active@INNATE_IMMUNE_CELL_Cytosol
→ IKBKG|ubi:IKK_beta_*|pho:MHC_class_I*@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K4|pho@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K3|pho@INNATE_IMMUNE_CELL_Cytosol