Identifiers
HUGO:MAP3K1
mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
HUGO:MAP3K1 HGNC:6848 ENTREZ:4214 UNIPROT:Q13233
MEKK1 "mitogen-activated protein kinase kinase kinase 1"
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
References
PMID:10465784 PMID:9582321 PMID:15170913 PMID:11668179 PMID:9379049 PMID:12048245
PMID:17496911
PMID:10465784
ECSIT (evolutionarilyconserved signaling intermediate inToll pathways), is specific for the Toll/IL-1 pathways and is a regulator of MEKK-1 processing. Expression of wild-type ECSIT accelerates processing of MEKK-1, whereas a dominant-negative fragment of ECSIT blocks MEKK-1 processing and activation of NF-??B
ECSIT mutant also strongly inhibited MEKK-1 activation of AP-1 (probably via MAP2K4/JNK),
additionally TRAF6-induced signaling is inhibited by dominant-negative constructs of MEKK-1.
PMID:9582321
DeltaMEKK1 overexpression results in activation of both c-Jun N-terminal kinases/extracellular signal-regulated kinases (JNK/SAPK) and p38 MAPK (non_immune model).
PMID:15170913, PMID:9582321, PMID:11668179
MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway upregulates COX2 expression and PGE2 production in macrophages,
via activation of transcription factor C/EBP beta.
PMID:9379049
MKK3 and MKK4 are capable of phosphorylating p38mapk in macrophages,
downstream of TNF/Tnf receptor signaling.
PMID:12048245
IFN-??-Induced Gene Expression is MEKK1/p38 dependent and MEKK1/ERK dependent
MEKK1 upregulates CEBPB activation via ERK
MEKK1 (MAP3K1) is a key MAP3K.
MEKK1 is significantly activated by TNF. Oligomerisation of TRAFs is sufficient to trigger MEKK1 binding. MEKK1 associates selectively with oligomerised TRAF2 in vivo in a TNF-dependent manner. MEKK1 can interact with Ras in a GTP-dependent manner. The GTP-dependent coupling of MEKK1 to Ras indicates that MEKK1 may be an effector for those agonists that recruit JNK through Ras-dependent mechanisms. MEKK1 selectively activates the endogenous JNK pathway. MEKK1 can activate MEK4 and MEK7 in vivo.
PMID:18855897 PMID:11274345
Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
References
rc_re1731:( Regulated Cell Death ) PMID:17496911
References
su_mpk1_mpk1_re137( Survival ):
MEKK1 can interact with Ras in a GTP-dependent manner. The GTP-dependent coupling of MEKK1 to Ras indicates that MEKK1 may be an effector for those agonists that recruit JNK through Ras-dependent mechanisms.
PMID:11274345
su_mpk1_mpk1_re138( Survival ):
MEKK1 is significantly activated by TNF. Oligomerisation of TRAFs is sufficient to trigger MEKK1 binding. MEKK1 associates selectively with oligomerised TRAF2 in vivo in a TNF-dependent manner.
→ MAP3K1@T_cell
→ MAP3K1@INNATE_IMMUNE_CELL_Cytosol
→ MAP3K1|pho@Cytosol
+ MAP3K1@Cytoplasm → GRB2:MAP3K1|pho:RAS*|pho:RTK*:SOS*@Cytoplasm
+ RIPK1:TNFRSF1A:TRADD:TRAF2@Plasma Membrane → MAP3K1|pho:RIPK1:TNFRSF1A:TRADD:TRAF2@Cytoplasm
+ TNFRSF1B:TRAF2@Plasma Membrane → MAP3K1|pho:TNFRSF1B:TRAF2@Cytoplasm
→ MAP2K4|pho@T_cell
→ MEK*|pho@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K4|pho@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K7|pho@Cytosol
→ MAP2K4|pho|pho@Cytoplasm
→ MAP2K7|pho|pho@Cytoplasm