Identifiers
HUGO:MAP2K4
mitogen-activated protein kinase kinase 4
HUGO:MAP2K4 HGNC:6844 ENTREZ:6416 UNIPROT:P45985
SERK1
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
Regulated Cell Death / MOMP_REGULATION
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
References
PMID:16076871
PMID:24104473 PMID:16799472 PMID:15735649
synonym:MKK4 synonym:MEK4
MACROPHAGE
CASCADE:TLR2_4
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:17379190
MEK4/JNK/AP-1 path way is active in mactophages downstream of TLR4,
and induces iNOS expression.
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.
MAP2K for JNK pathway. MEK4 is weakly activated by TNF and IL-1.
PMID:11274345
References
ad_re361:( Adaptive Immune Response ) PMID:16713974 PMID:11438547 PMID:24378531
References
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.
PMID:11438547, PMID:24378531
Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation.
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.
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
References
su_mpk1_mpk1_re153( Survival ):
MLK3 and MLK2 two MAP3Ks of JNK pathway can interact with RAC1 in a GTP-dependent manner.
MEKK2 and MEKK3 can activate JNK P38 and ERK pathways.
TAO kinases are novel MAP3Ks that specifically regulate P38s.
ASK1 is a MAP3K and can activate both JNK and P38 pathways.
MEKK1 selectively activates the endogenous JNK pathway. MEKK1 can activate MEK4 and MEK7 in vivo.
MEKK4 is a MAP3K and can activate both JNK and P38 pathways.
TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways.
Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6.
MLK3 has the potential to positively regulate the ERK / MAPK pathway by directly phosphorylating and activating MEK.
Expression of GADD45 genes in mammalian cells strongly activates co-expressed MTK1 as well as P38 and JNK the MAPKs downstream of MTK1. TAO kinases are MAP3Ks that function upstream of P38 and JNK.
PMID:11274345 PMID:12738796 PMID:18855897 PMID:21614932
References
su_mpk1_mpk1_re153( Survival ):
MLK3 and MLK2 two MAP3Ks of JNK pathway can interact with RAC1 in a GTP-dependent manner.
MEKK2 and MEKK3 can activate JNK P38 and ERK pathways.
TAO kinases are novel MAP3Ks that specifically regulate P38s.
ASK1 is a MAP3K and can activate both JNK and P38 pathways.
MEKK1 selectively activates the endogenous JNK pathway. MEKK1 can activate MEK4 and MEK7 in vivo.
MEKK4 is a MAP3K and can activate both JNK and P38 pathways.
TAK1 is a MAP3K. It is able to activate both JNK and P38 pathways.
Endogenous TAK1 is activated by TGF-beta IL-1 and TNF. TAK1 can phosphorylate and activate MEK4 MEK3 and MEK6.
MLK3 has the potential to positively regulate the ERK / MAPK pathway by directly phosphorylating and activating MEK.
Expression of GADD45 genes in mammalian cells strongly activates co-expressed MTK1 as well as P38 and JNK the MAPKs downstream of MTK1. TAO kinases are MAP3Ks that function upstream of P38 and JNK.
PMID:11274345 PMID:12738796 PMID:18855897 PMID:21614932
su_mpk1_mpk1_re156( Survival ):
MEK4 and MEK7 can activate all JNK isoforms (by phosphorylation).
PMID:11274345
→ MAP2K4|pho@T_cell
→ MAP2K4|pho@Cytosol
→ MAP2K4|pho@INNATE_IMMUNE_CELL_Cytosol
→ MAP2K4|pho@Cytosol
→ MAP2K4|pho|pho@Cytoplasm
→ JNK*|pho|active@T_cell
→ p38*|Tyr180_pho|TYR182_pho|active@T_cell
→ JNK1*|pho@Cytosol
→ JNK2*|pho@Cytosol
→ JNK*|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ p38*|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ JNK*|Y185_pho@Cytosol
→ p38*|T180_pho|Y182_pho@Cytosol
→ JNK*|pho|pho@Cytoplasm