Identifiers
NAME:MAP3K7:TAB2:TAB3
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
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:14660645, PMID:18264787, PMID:11460167
Activated TAK1 phosphorylates IKK-beta proteins
leading to activation of NF-??B downstream of HMGB1.
PMID:23681101, PMID:11477091
There are three main signaling pathways could be activated downstream of TRR4/MyD88/TAK1 signaling??: p38 (via MKK3 or MKK6), JNK (via MKK4 or MKK7) and NfkB ) IN DC all these signaling pathways are activated downstream of TLR4 and TLR2 signaling )
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.
in_re884( Innate Immunity ):
PMID:21232017, PMID:21133840, PMID:17301840
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