Identifiers
HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1
mitogen-activated protein kinase 3
HUGO:MAPK3 hgnc_id:HGNC:6877 HGNC:6877 ENTREZ:5595 UNIPROT:P27361
DSN1 homolog, MIS12 kinetochore complex component
HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410
mitogen-activated protein kinase 1
HUGO:MAPK1 hgnc_id:HGNC:6871 HGNC:6871 ENTREZ:5594 UNIPROT:P28482
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CORE
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
References
PMID:10811803 PMID:24027568 PMID:10807788 PMID:9510155 PMID:11262396 PMID:10898494 PMID:14764585 PMID:22043013 PMID:26552706
KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3
REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1
CASCADE:MIF
CASCADE:TNF
CASCADE:FGF
CASCADE:EGFR
CASCADE:TGFB
GASCADE:IGF1R
PMID:12782713
CD74 mediates MIF stimulation of ERK-1/2 (p44/p42) phosphorylation and proliferation of CCL210 human lung fibroblasts.
PMID:15653932
TNF signaling activates ERK,JNK and p38 kinases in fibroblasts and induses TGFB expression
via ERK
PMID:22652804
TGF-??1 CM enhanced fibroblast proliferation and
differentiation. FGF-2 is
necessary for the fibroblast proliferation induced by TGF.
. Fibroblast ERK signaling is required for TGF-??1
CM-induced cell differentiation and proliferation
PMID:25374926
TGFB induces FGF2 expression and secretion in fibroblasts via SMAD3 and MAPK pathways (erk,p38)
PMID:23010081
FGF2 and EGF signalings act via ERK1/2 in fibroblasts
PMID:24782617
IGFR pathway is imporatnd for fibroblast activation.
IGF-1-induced collagen I expression was mediated by extracellular signal-regulated kinase 1/2
(ERK1/2)-dependent mechanism.
PMID:10567412; PMID:15567848
EGFR activates ERK via GRB2/SOS/RAS/RAF pathway
NATURAL_KILLER
DENDRITIC_CELL
MACROPHAGE
NEUTROPHIL
CASCADE:VEGFA
CASCADE:NKP80
CASCADE:KIR2DS4
CASCADE:NKP46
CASCADE:Fc_gamma_RIII
CASCADE:LFA1
CASCADE:INTEGRIN_A4B1
CASCADE:INTEGRIN_A5B1
CASCADE:TLR2_4
CASCADE:IL15
CASCADE:IL2
CASCADE:IFNG
PMID:11062502, PMID:11385609, PMID:11907067, PMID:15536084
Nkp46 controls NK cytolitic activity via PI3K /RAC1/PAK1/MEK??/ERK pathway, probably throught SYK
PMID:17395718, PMID:11062502, ??PMID:15536084
PAK1 activates classical MEK/ERK cascad resulted in granule movement and polarization and tumor cel lysis downstream of Nkp30, Syk and PI3K.
PMID:11062502, PMID:15536084
ERK1/2 activation induces perforin and granzyme B movement towards target tumor cells downstream of PI3K signaling in NK cells.
PMID:21149606
NKp80 activates PI33/ERK pathway probably via SYK.
PMID:22786724
DNAM1 induces ERK pathway probably via VAV1.
PMID:20189481
PLCG inhibitor completely abrogated synergistic Erk phosphorylation downstream of NKG2D and 2B4.
These data suggest that PLCG, rather than PI3K, is a critical upstream regulator of Erk activation in this pathway.
PMID:10849428
IL-2 and IL-15 are able to induce the phosphorylation of ERK1/2. probably via PI3K pathway.
MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-gamma secretion, and IL2RA (CD25) and CLEC2C(CD69) expression.
PMID:10903731
IL18 signaling induces activation of ERK1/2 kinases. The cytolytic activity of NK cells downstream of IL18
is inhibited by ERK inhibitors.
PMID:20363967, PMID:16204085
Src homology 2-containing inositol 5'-phosphatase 1 negatively regulates IFN-gamma production by natural killer cells stimulated with antibody-coated tumor cells and interleukin-12, probably via inhibition of PI3K pathway and downstream ERK signaling.
PMID:15563472
Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells.
PMID:11489965, PMID:10843677
The IFN-?? secretion by NK cells induced by IL-2 depends on an ERK mitogen-activated protein kinase pathway.
IL-2 activation of an MKK/ERK pathway is required for NK cells to acquire enhanced cytolytic function (LAK activity).
IL-2-driven IFN-?? secretion and induction of CD25 and CD69 (CLEC2C) activation markers require intact MKK/ERK pathway.
PMID:9862693
CD16-induced ERK activation provides IFN-?? mRNA accumulation and ADCC and spontaneous cytotoxicity of NK cells
PMID:9064320
CD16-induced ERK activation provides TNFA expression in NK cells.
MEK/ERK cascade induces AP1(c-fos) phosphorylation downstream of CD16
PMID:9120268, PMID:9973479
ERK2 activates Phospholipase A2 group IIA (sPLA2 and cPLA2) by phosphorylation downstream of CD16 activation, but CDl6-induced degranulation in human NK cells is
dependent on ERK activation, but not on sPLA, or cPLA.
PMID:10679059, PMID:12626562
PTK2B, PYK2. Binding of NK cells to sensitive target cells or ligation of ??2 integrins results in a rapid induction of Pyk2 phosphorylation and activation.
y contrast, no detectable Pyk2 tyrosine phosphorylation is found upon CD16 stimulation.
Pyk2 activation is a crucial event for natural but not Ab-dependent cytotoxicity.
Ligation of Beta2 integrins on NK cells resulted in Pyk2-dependent Erk activation, provavli via VAV1/RAC1 pathway.
Pyk-2-mediated control of integrin-triggered Rac-1 activation involves the regulation of Vav tyrosine phosphorylation.
PMID:9763606
Cross-linking of ??1 Integrins on Human NK Cells Induces Shc Tyrosine Phosphorylation and Grb2 Association via Pyk-2end
resulted in RAS/ERK activation. Integrin-mediated Ras???Extracellular Regulated Kinase (ERK) Signaling Regulates Interferon ?? Production in Human Natural Killer Cells.
PMID:15113754
LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells.
(ICAM-2) and ICAM-3 promoted LFA-1-directed perforin release, whereas ICAM-1 had little effect.
PMID:12048245
IFN-??-Induced Gene Expression is MEKK1/p38 dependent and MEKK1/ERK dependent
MEKK1 upregulates CEBPB activation via ERK
PMID:10733514
ERK2 activated MLCK, resulting in phosphorylation of the MLCK substrate or of the myosin light chain itself.
And induces phagocytosis.
PMID:17086423
VEGF treatment enhanced the phospho-Erk 1 and 2 via KDR in DC
MIF signal transduction initiated by binding to CD74.
CD74 Mediates MIF Induction of ERK-1/2 Phosphorylation, PGE2 Production, and Proliferation in macrophages.
PMID:23508573
HMGB1 induces activation (phosphorylation) of ERK, JNK and p38 via TLR4 in macrophages
PMID:16713974, PMID:11579131
INFG pathway inhibits activation (phosphorylation) of ERK, JNK, p38 kinases and PI3K pathway induced by TLR. Inhibition of AKT pathway by IFNG resulted in activation of GSK3. GSK3 inhibits downstream AP-1 and CREB1 signaling and downregulates IL10 expression induced by TLR.IFNG inhibits CREB activation via p38 induced by TLR signaling
PMID:21826665
ERK is activated in TAN
References
in_re869( Innate Immunity ):
PMID:16327802
IL13 and TNF inducese TGFB1 expression via AP-1 transcription factors.IL13 induces binding of c-jun and fra2 ti TGFB1 promotor, and TNF binding of c-jun, JunD and c-fos.
in_re870( Innate Immunity ):
PMID:16713974
INFG signaling ingibits FOS expression
in_re1031( Innate Immunity ):
PMID:12907458
Bcl-3??? ???interacted with NF-??B p50,
both Bcl-3??? ???and p50??? ???were recruited to the TNF promoter,
BCL3??? ??? and??? ???p50??? ???NFkB recruitment to??? ???TNF ???promoter
prevents binding of??? ???p65/p50??? ???NFkB??? ???heterodimers
to??? ???TNF promotor and suppresses??? ???TNF ???expression
downstream of??? ???IL10.
PMID:17485448
Inhibition of??? ???NFkB signaling downstream of??? ???ABIN3??? ???
inhibits expression of??? ???IL8,??? ???IL6,??? ???TNF,??? ???IL12.
PMID:15465827
BCL3 forms complex with HDAC1 and
repression of the TNF promoter by BCL3
requires Histone Deacetylase Activity.
BCL3 inhibits expression of TNF.
PMID:11875494
HMOX1 (HO1) mediates IL-10-induced suppression of TNF production.
PMID:16878026, PMID:14660645, PMID:15644117, PMID:10952726
Increased TNF expression downstream of HMGB1 is regulated via MYD88 and probably NFkB.
PMID:10754326
Human TNF-alpha gene has binding sites for NF-kappa B. By transient transfection,
NF-kappa B p65 and p50 synergistically activated the TNF-alpha promoter.
Although both the kappa B1 and kappa B3 sites bound transcriptionally active NF-kappa B p50/p65 heterodimers, only the kappa B1 site contributed to down-regulation by NF-kappa B p50 homodimers.
PMID:17404308
CSF1 downregulates TNF, IL-23p19, IL-12p40 expression probably via induction of acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling.
CSF2 upregulates expression of TNF, and have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling.
PMID:7594497
TGFB1 and IL10 dowregulate expression of TNF.
PMID:23390297
MIF inhitits expression of M1 markers such as TNF.
in_re1149( Innate Immunity ):
GSK3B inhitits activation (DNA binding) of AP-1 factors.
JNK is a classical activator of AP1 transcription factors.
Inhibition of JNK downregulates IL10 expression. Probably via
AP1.
→ rTNF@INNATE_IMMUNE_CELL_Cytosol
→ IFNG@default
→ PRF1@default
→ AP1*|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ MNK1|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ PLA2G2A|pho@INNATE_IMMUNE_CELL_Cytosol
→ PLA2G4A|pho@INNATE_IMMUNE_CELL_Cytosol
→ rIFNG@INNATE_IMMUNE_CELL_Cytosol
→ FOS|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ rFOS@INNATE_IMMUNE_CELL_Cytosol
→ CEBPB|pho@INNATE_IMMUNE_CELL_Cytosol
→ MLCK*|pho@INNATE_IMMUNE_CELL_Cytosol