p38*

Protein p38*

Identifiers
HUGO:MAPK14
HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14
REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11
REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12
REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13
REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14
mitogen-activated protein kinase 11
HUGO:MAPK11 hgnc_id:HGNC:6873 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759
DSN1 homolog, MIS12 kinetochore complex component
HUGO:DSN1 hgnc_id:HGNC:16165 HGNC:16165 ENTREZ:79980 UNIPROT:Q9H410
mitogen-activated protein kinase 12
HUGO:MAPK12 hgnc_id:HGNC:6874 HGNC:6874 ENTREZ:6300 UNIPROT:P53778
mitogen-activated protein kinase 13
HUGO:MAPK13 hgnc_id:HGNC:6875 HGNC:6875 ENTREZ:5603 UNIPROT:O15264
mitogen-activated protein kinase 14
HUGO:MAPK14 hgnc_id:HGNC:6876 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539
HUGO:MAPK11 HGNC:6873, ENTREZ:5600 , UNIPROT:Q15759
HUGO:MAPK12 HGNC:6874, ENTREZ:6300 , UNIPROT:P53778
HUGO:MAPK13 HGNC:6875, ENTREZ:5603 , UNIPROT:O15264
HUGO:MAPK14 HGNC:6876, ENTREZ:1432, UNIPROT:Q16539
PRKM11
SAPK3
PRKM13
CSBP1 CSBP2 CSPB1
HUGO:MAPK11 HGNC:6873 ENTREZ:5600 UNIPROT:Q15759 GENECARDS:MAPK11 REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11
HUGO:MAPK12 HGNC:6874 ENTREZ:6300 UNIPROT:P53778 GENECARDS:MAPK12 REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12
HUGO:MAPK13 HGNC:6875 ENTREZ:5603 UNIPROT:O15264 GENECARDS:MAPK13 REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13
HUGO:MAPK14 HGNC:6876 ENTREZ:1432 UNIPROT:Q16539 GENECARDS:MAPK14 REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14
Mxi2 P38 "P38 MAP kinase" PRKM14 PRKM15

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CORE
EMT Senescence / EMT_REGULATORS
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
Survival / WNT_CANONICAL
Survival / WNT_NON_CANONICAL

References
PMID:11532940
PMID:10395678
TCR and CD28 Are Coupled Via ZAP-70 to the Activation of the Vav/Rac-1-/PAK-1/p38 MAPK Signaling Pathway
PMID:15735648
T cell Src family kinases (lck and fyn) and Zap70 activate p38 by phosphorylating Tyr323 downstream of TCR.
Lck is required for activation of Zap70, which in turn phosphorylates and activates p38.
PMID:16799472
GADD45 inhibited p38 activated by ZAP70 (that is, through phosphorylation of Tyr323) but not by MKK6 (that is, through phosphorylation of Thr180 and Tyr182).
PMID:24104473
Triggering of the T cell receptor (TCR) activates Src family kinases (SFK) and the zeta-chain-associated protein of 70 kDa (ZAP-70). These tyrosine kinases lead to the activation of the transcription factor NF-??B and the p38 mitogen-activated protein kinase. NF-??B induces transcription of the Gadd45b gene. The same applies to the cytokines IL-12 and IL-18 as well as stimulation of the Notch receptor and its cytoplasmic effector Deltex. The cytokine IL-2 activates transcription of the Gadd45g gene. Both Gadd45?? and Gadd45?? proteins interact with the kinase MEKK4, which leads to sustained p38 activation and, subsequently, to interferon-?? (IFN-??) production and Th1 differentiation.
PMID:11371360
p38 and JNK pathways are very important for the responses of TH1 effector cells (Lu et al., 1999; Rincon et al., 1998; Yang et al., 1998). The p38 kinase can be activated efficiently in TH1 effector cells but not in TH2 effector cells; blocking the pathway inhibits and agonists of the pathway potentiate TH1 responses
PMID:11175814
IL-12 + IL-18 induces expression of GADD45B and GADD45G mRNA in TH1 cells.
GADD45B significantly increased phosphorylated p38 MAPK compared to the control
MEKK4-p38 pathway is requied for INFG transcription activation downstream IL12 and IL18
IL-18 induction of GADD45B by NF-B and a requirement for GADD45 interaction with MEKK4 in the downstream induction of IFNG
PMID:16200688; PMID:15282297
Phosphorylation of p38 after TCR stimulation was enhanced in anergic CD4+ T cells over that in naive CD4+ T cells, which showed limited phosphorylation. In contrast, the phosphorylation of ERK and JNK in anergic CD4+ T cells was severely reduced, consistent with the previous report of T cells that were anergized in vitro
T-cell proliferation is inhibited by p38 MAPK activity in anergic CD4+ T cells.
The production of IL-2 is inhibited by p38 activity in anergic CD4+ T cells, while IL-10 production is p38 dependent
REACTOME:59299 KEGG:5600 ATLASONC:GC_MAPK11 WIKI:MAPK11
REACTOME:69723 KEGG:6300 ATLASONC:MAPK12ID41290ch22q13 WIKI:MAPK12
REACTOME:59303 KEGG:5603 ATLASONC:MAPK13ID41291ch6p21 WIKI:MAPK13
REACTOME:405912 KEGG:1432 ATLASONC:MAPK14ID41292ch6p21 WIKI:MAPK14
CASCADE:TNF
CASCADE:TGFB
CASCADE:PDGFB
PMID:15653932
TNF signaling activates ERK,JNK and p38 kinases in fibroblasts and induses TGFB expression
via ERK
PMID:25374926
TGFB induces FGF2 expression and secretion in fibroblasts via SMAD3 and MAPK pathways (erk,p38)
PMID:26921338
PDGFB inhibits PEDF expression via p38 and JNK
synonym:p38_beta_
synonym:p38_gamma_
synonym:p38_delta_
synonym:p38
PMID:11238627
SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-??.
PMID:11489965
The induction by KIR2DL4 of IFN-gamma production by resting NK cells was blocked by an inhibitor of the p38 mitogen-activated protein kinase signaling pathway
PMID:10961885, PMID:15345584, PMID:10903731
IL-12 and IL18 activate p38 in NK cells.
IFNG mRNA is stabilized by MAPK p38.
MAPK p38 signaling downstream of IL18 and IL 12 increases IFNG production.
PMID:10661401
MKK3 is activated by ??1 Integrin Cross-Linking on Human NK Cells,
It activates p38MAPK regulated IL8 production by NK cells downstream of integrin signaling.
PMID:9379049
MKK3 and MKK4 are capable of phosphorylating p38mapk in macrophages,
downstream of TNF/Tnf receptor signaling.
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 factors C/EBP beta and CEBPD.
PMID:12048245
IFN-??-Induced Gene Expression is MEKK1/p38 dependent and MEKK1/ERK dependent
MEKK1 upregulates CEBPB activation
PMID:11875494
IL10 stimulates HO1 expression via MAPK p38 stimulation. HO-1 mediates IL-10-induced suppression of TNF- production and IL-10-induced suppression of MMP9 expression.
PMID:22955274
SHIP inhibit MAPKp38 activation and prevent MNK1 phosphorylation by inhibiting the p38 MAPK pathway downstream of IL10. MNK1 regulates TNFa mRNA polysome assembly and upregulates TNFa translation.IL-10 Inhibits TNF Translation through SHIP1-mediated Inhibition of Mnk1
PMID:17073741
DUSP1 inhibits p38 and JNK pathways of innate innunity
PMID:16184516
Increased expression of DUSP1 in IL-10-treated activated macrophages was correlated with a faster down-regulation of p38 MAPK activation.
PMID:10606755
LPS and TNFalpha were found to induce the expression of SOCS3 mRNA in each of the investigated type of macrophages but not in HepG2 cells. Using a specific inhibitor, evidence is presented that the p38 MAP kinase might be involved, especially for the inhibitory effect of TNFalpha.
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:23508573
HMGB1 induces activation (phosphorylation) of ERK, JNK and p38 via TLR4 in macrophages
PMID:11438547, PMID:24378531
in macrophages
Both TNFR1 and TNFR2 signaling pathways induce classical NFkB activation via IKBa degradation.
Both TNFR1 and TNFR2 signaling pathways induce JNK activation and downstrean c-jun phosphorylation.
Both TNFR1 and TNFR2 signaling pathways are needed for activation of p38 MAPK.
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

p38*|Tyr323_pho@T_cell

References
ad_re383( Adaptive Immune Response ):
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.
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 are needed for activation of p38 MAPK.

p38*@T_cell

p38*|pho|active@Cytosol

References
ca_re284( Cancer Associated Fibroblasts ):
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.
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 are needed for activation of p38 MAPK.

p38*@Nucleus

References
em_emtc_emtc_re1186( EMT Senescence ):
PMID:21502402
Phosphorylation of serine 68 of Twist1 stabilizes Twist1 protein and promotes breast cancer cell invasiveness.
Twist1 can be phosphorylated in vitro at Serin 68 by MAPKs (p38MAPKs, JNKs, ERK1/2)
This phosphorylation is required for Twist1 protein stability.
pSer 68 stabilizes Twist1 by protecting Twist1 from ubiquitination
Ser 68 phosphorylation is required for Twist1- promoted EMT and breast cancer cell invasion

p38*|T180_pho|Y182_pho@Cytosol

Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS

References
rc_re498( Regulated Cell Death ):
PMID:12792650
Direct phosphorylation of CASP9 by ERK2 sufficient to block CASP9 processing
in vitro, recombinant hCASP9 phosphorylated on T125 by cytosolic extract or ERK2
in Hela cells, interaction GST-CASP9 / ERK
in Hela or HEK293, CASP9 T125 phosphorylation by OA, consititutively active MEK1, EGF or TPA
PMID:17466630
CASP9 T125 phosphorylation by CCNB1:CDC2
comment: phosphorylation during mitosis, when nuclear envelope is broken down
PMID:19081073
CASP9 T125 phosphorylation by DYRK1A
PMID:19016842
PMID:19586613
CASP9 T125 phosphorylation by DYRK1A and p38
rc_re1323( Regulated Cell Death ):
PMID:11359773
by DUSP16

p38*@INNATE_IMMUNE_CELL_Cytosol

p38*|pho|active@INNATE_IMMUNE_CELL_Cytosol

References
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.
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 are needed for activation of p38 MAPK.
in_re559( Innate Immunity ):
PMID:17485448
Inhibition of??? ???NFkB signaling downstream of??? ???ABIN3??? ???
inhibits expression of??? ???IL8,??? ???IL6,??? ???TNF,??? ???IL12
in_re1085( Innate Immunity ):
IL10 stimulates HMOX1 (HO1) expression via MAPK p38 stimulation.
IL-10-mediated increase in HMOX1 mRNA level was completely
blocked by SB203580, a specific inhibitor of p38.
in_re1088( Innate Immunity ):
PMID:12907458
IL10 induces SOCS3 expression in STAT3 dependent manner.
in_re1281( Innate Immunity ):
TLR activation of CREB by phosphorylation of serine-133 is dependent on p38.
GSK3B inhibits IL10 expression downstream of IFNG, probably via GREB1 inhibition.
PMID:16007092
GSK3B inhibits CREB1 interaction CBP and inhibits CREB1 dependent IL10 expression.

p38*@Cytoplasm

References
su_wnc1_s_wnc2_re78:( Survival ) PMID:16648474
su_mpk1_mpk1_re65( Survival ):
Mxi2 is a splicing isoform of P38. It directly interacts with ERK1/2. Mxi2 prolongs ERK activation (in the nucleus) by binding.
Mxi2 could suffice to promote the transport of ERK1/2 to the nucleus in the absence of further stimulation.
PMID:12697810 PMID:17255949
su_mpk1_mpk1_re155( Survival ):
MEK3 and MEK6 are high selective for P38 activation (by phosphorylation).
PMID:11274345
su_wnc1_s_wnc2_re82( Survival ):
Most likely, the complex will dissociates
PMID:16648474
su_wca1_s_wca3_re96( Survival ):
Allosteric effect
PMID:10747897
su_wca1_s_wca3_re101( Survival ):
References_begin
PMID:15649893

p38*|pho|pho@Cytoplasm

References
su_mpk1_mpk1_re155( Survival ):
MEK3 and MEK6 are high selective for P38 activation (by phosphorylation).
PMID:11274345
su_mpk1_mpk1_re163( Survival ):
MAPKAPK2 and MAPKAPK3 are phosphorylated and activated by P38alpha and P38 beta.
su_mpk1_mpk1_re165( Survival ):
MNKs are cytoplasmic targets of ERK and P38.
PMID:15187187
su_mpk1_mpk1_re166( Survival ):
MAX is phosphorylated by P38 through complex formation (not represented here).
su_mpk1_mpk1_re182:( Survival ) Nuclear shuttling of activated P38 is assumed similarly to ERK.
su_mpk1_mpk1_re187( Survival ):
JNK pathway negatively regulates ERK pathway by uncoupling ERK activation from MEK via activation of JUN transcriptional activity.
A direct interaction between P38 and ERK has been proposed as a mechanism to inhibit ERK phosphorylation. AP-1 mediated gene expression inhibits ERK phosphorylation.
PMID:12738796 PMID:18039929
su_mpk1_mpk1_re189( Survival ):
MEK is continuously dephosphorylated by PP2A (PPP2CA) whose activity is stimulated by P38: P38 activity increases the physical association between PP2A and MEK/ERK complex. A direct interaction between P38 and ERK has been proposed as a mechanism to inhibit ERK phosphorylation. AP-1 mediated gene expression inhibits ERK phosphorylation.
PMID:18039929
su_mpk1_mpk1_re194( Survival ):
MEK is continuously dephosphorylated by PP2A (PPP2CA) whose activity is stimulated by P38: P38 activity increases the physical association between PP2A and MEK/ERK complex.

p38*|pho|pho@Nucleus

References
su_mpk1_mpk1_re182:( Survival ) Nuclear shuttling of activated P38 is assumed similarly to ERK.
su_mpk1_mpk1_re91( Survival ):
The rapid and efficient phosphorylation of Elk1 by ERKs is enabled by a direct interaction between the two proteins.
ELK1 is a nuclear P38 target.
ELK1 is a nuclear JNK target.
PMID:16393692 PMID:20506250 PMID:11274345
su_mpk1_mpk1_re95( Survival ):
MSK1 and MSK2 are potently activated (by phosphorylation) in vivo by ERK1/2 and P38 but not JNK. They are localised in the nucleus of quiescent and activated cells which suggest that they may preferentially phosphorylate nuclear substrates.
PMID:15187187
su_mpk1_mpk1_re168( Survival ):
P38 and not JNK or ERK can phosphorylate CHOP/GADD153 (DDIT3).
PMID:11274345
su_mpk1_mpk1_re176( Survival ):
ATF2 is a nuclear P38 target.
ATF2 is a nuclear JNK target.
PMID:20506250 PMID:11274345
su_mpk1_mpk1_re179( Survival ):
P53 is a nuclear P38 target.
Activated P38 phosphorylates P53 at several residues including Ser33 and thereby increases the transcriptional activity of P53.
ATM phosphorylates P53 at ser15 and stabilize it.
PMID:20506250 PMID:21614932 PMID:15140942
su_mpk1_mpk1_re181( Survival ):
MKP-1 (DUSP1) preferentially inactivates JNK and P38.
PMID:19436832

Modifications:
In compartment: Cytoplasm

p38*@Cytoplasm
p38*@Cytoplasm
p38*@Cytoplasm
p38*|pho|pho@Cytoplasm

In compartment: Cytosol

p38*@Cytosol
p38*|pho|active@Cytosol
p38*|T180_pho|Y182_pho@Cytosol

In compartment: INNATE_IMMUNE_CELL_Cytosol

p38*@INNATE_IMMUNE_CELL_Cytosol
p38*|pho|active@INNATE_IMMUNE_CELL_Cytosol

In compartment: Nucleus

p38*@Nucleus
p38*|pho|pho@Nucleus

In compartment: T_cell

p38*@T_cell
p38*|Tyr323_pho@T_cell
p38*|Tyr180_pho|TYR182_pho|active@T_cell
p38*|Tyr323_pho|Tyr180_pho|TYR182_pho|active@T_cell

Participates in complexes:
In compartment: Nucleus

DUSP1:p38*@Nucleus

Participates in reactions:
As Reactant or Product:

As Catalyser: