Product: Phospho-p38 MAPK (Thr180/Tyr182) Antibody
Catalog: AF4001
Source: Rabbit
Application: WB, IHC, IF/ICC, IP, ELISA(peptide)
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Xenopus
Mol.Wt.: 43 kD; 41kD(Calculated).
Uniprot: Q16539
RRID: AB_2835330

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 100ul $350 In stock
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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:200, IP, ELISA(peptide) 1:20000-1:40000
*The optimal dilutions should be determined by the end user.
Reactivity:
Human,Mouse,Rat
Prediction:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Xenopus(91%)
Clonality:
Polyclonal
Specificity:
Phospho-p38 MAPK (Thr180/Tyr182) Antibody detects endogenous levels of p38 MAPK only when phosphorylated at Thr180 and Tyr182 .
RRID:
AB_2835330
Cite Format: Affinity Biosciences Cat# AF4001, RRID:AB_2835330.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

CSAID Binding Protein 1; CSAID binding protein; CSAID-binding protein; Csaids binding protein; CSBP 1; CSBP 2; CSBP; CSBP1; CSBP2; CSPB1; Cytokine suppressive anti-inflammatory drug-binding protein; EXIP; MAP kinase 14; MAP kinase MXI2; MAP kinase p38 alpha; MAPK 14; MAPK14; MAX interacting protein 2; MAX-interacting protein 2; Mitogen Activated Protein Kinase 14; Mitogen activated protein kinase p38 alpha; Mitogen-activated protein kinase 14; Mitogen-activated protein kinase p38 alpha; MK14_HUMAN; Mxi 2; MXI2; p38 ALPHA; p38; p38 MAP kinase; p38 MAPK; p38 mitogen activated protein kinase; p38ALPHA; p38alpha Exip; PRKM14; PRKM15; RK; SAPK2A;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
Q16539 MK14_HUMAN:

Brain, heart, placenta, pancreas and skeletal muscle. Expressed to a lesser extent in lung, liver and kidney.

Description:
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines.
Sequence:
MSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Horse
100
Bovine
100
Sheep
100
Dog
100
Rabbit
100
Xenopus
91
Zebrafish
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - Q16539 As Substrate

Site PTM Type Enzyme
S2 Acetylation
S2 Phosphorylation
T7 Phosphorylation
K15 Ubiquitination
T16 Phosphorylation
S28 Phosphorylation
S32 Phosphorylation
K45 Ubiquitination
K53 Acetylation
K54 Ubiquitination
S56 Phosphorylation
S61 Phosphorylation
K66 Ubiquitination
K79 Sumoylation
K79 Ubiquitination
K118 Ubiquitination
K121 Ubiquitination
T123 Phosphorylation P25098 (GRK2)
K139 Ubiquitination
S143 Phosphorylation
K152 Acetylation
K152 Ubiquitination
K165 Ubiquitination
T175 Phosphorylation
T180 Phosphorylation P46734 (MAP2K3) , P52564 (MAP2K6) , P07949 (RET) , P45985 (MAP2K4) , Q99683 (MAP3K5) , O95382 (MAP3K6) , Q16539 (MAPK14)
Y182 Phosphorylation P52564 (MAP2K6) , O95382 (MAP3K6) , P45985 (MAP2K4) , Q16539 (MAPK14) , O14733-2 (MAP2K7) , Q99683 (MAP3K5) , P46734 (MAP2K3) , P07949 (RET)
T185 Phosphorylation
K233 Ubiquitination
T241 Phosphorylation
K248 Ubiquitination
K249 Ubiquitination
R256 Methylation
T263 Phosphorylation
K295 Ubiquitination
Y323 Phosphorylation P06241 (FYN) , P06239 (LCK) , P43403 (ZAP70)
S326 Phosphorylation
K338 Sumoylation
S339 Phosphorylation

PTMs - Q16539 As Enzyme

Substrate Site Source
F1D8S2 (NR2A1) S167 Uniprot
O00418 (EEF2K) S396 Uniprot
O15198 (SMAD9) T136 Uniprot
O43255 (SIAH2) S28 Uniprot
O43257 (ZNHIT1) T103 Uniprot
O43521 (BCL2L11) S69 Uniprot
O43524 (FOXO3) S7 Uniprot
O43524 (FOXO3) S12 Uniprot
O43524 (FOXO3) S294 Uniprot
O43524 (FOXO3) S344 Uniprot
O43524 (FOXO3) S425 Uniprot
O60381 (HBP1) S402 Uniprot
O75030 (MITF) S414 Uniprot
O75582 (RPS6KA5) S360 Uniprot
O75582-1 (RPS6KA5) S376 Uniprot
O75582 (RPS6KA5) T581 Uniprot
O75582 (RPS6KA5) T700 Uniprot
O75676 (RPS6KA4) S196 Uniprot
O75676-2 (RPS6KA4) S343 Uniprot
O75676-2 (RPS6KA4) S347 Uniprot
O75676 (RPS6KA4) S360 Uniprot
O75676-2 (RPS6KA4) T562 Uniprot
O75676 (RPS6KA4) T568 Uniprot
O95644 (NFATC1) S172 Uniprot
P00533 (EGFR) T693 Uniprot
P00533 (EGFR) S1039 Uniprot
P00533 (EGFR) T1041 Uniprot
P02511 (CRYAB) S59 Uniprot
P03372 (ESR1) S118 Uniprot
P03372 (ESR1) S294 Uniprot
P03372-1 (ESR1) T311 Uniprot
P04150 (NR3C1) S203 Uniprot
P04150 (NR3C1) S211 Uniprot
P04150 (NR3C1) S226 Uniprot
P04637 (TP53) S15 Uniprot
P04637 (TP53) S33 Uniprot
P04637 (TP53) S46 Uniprot
P04637-1 (TP53) S392 Uniprot
P04792 (HSPB1) S176 Uniprot
P05198 (EIF2S1) S52 Uniprot
P05787-1 (KRT8) S74 Uniprot
P06400 (RB1) S567 Uniprot
P06702 (S100A9) T113 Uniprot
P10275 (AR) S651 Uniprot
P10415 (BCL2) T56 Uniprot
P10415 (BCL2) S87 Uniprot
P10636-8 (MAPT) T50 Uniprot
P10636-8 (MAPT) T69 Uniprot
P10636-8 (MAPT) T153 Uniprot
P10636-8 (MAPT) S202 Uniprot
P10636-8 (MAPT) T205 Uniprot
P10636-8 (MAPT) S235 Uniprot
P10636-8 (MAPT) S404 Uniprot
P10636-8 (MAPT) S422 Uniprot
P11362 (FGFR1) S777 Uniprot
P13726 (F3) S285 Uniprot
P13726 (F3) S290 Uniprot
P14598 (NCF1) S345 Uniprot
P14598 (NCF1) S348 Uniprot
P15336 (ATF2) T69 Uniprot
P15336 (ATF2) T71 Uniprot
P15336-1 (ATF2) S90 Uniprot
P15923 (TCF3) S139 Uniprot
P16220 (CREB1) S133 Uniprot
P16949 (STMN1) S25 Uniprot
P17181 (IFNAR1) S532 Uniprot
P17275 (JUNB) S79 Uniprot
P17275 (JUNB) T102 Uniprot
P17275 (JUNB) T104 Uniprot
P17302 (GJA1) S279 Uniprot
P17302 (GJA1) S282 Uniprot
P17844 (DDX5) T446 Uniprot
P17844 (DDX5) T564 Uniprot
P17861 (XBP1) S68 Uniprot
P18850 (ATF6) T166 Uniprot
P19419 (ELK1) S383 Uniprot
P19419 (ELK1) S389 Uniprot
P19525 (EIF2AK2) T451 Uniprot
P19634 (SLC9A1) T718 Uniprot
P19634 (SLC9A1) S723 Uniprot
P19634 (SLC9A1) S726 Uniprot
P19634-1 (SLC9A1) S729 Uniprot
P21397 (MAOA) S209 Uniprot
P21462 (FPR1) S342 Uniprot
P22415 (USF1) T153 Uniprot
P28324 (ELK4) S381 Uniprot
P28324 (ELK4) S387 Uniprot
P28698 (MZF1) S256 Uniprot
P28698 (MZF1) S274 Uniprot
P28698 (MZF1) S294 Uniprot
P29353 (SHC1) S36 Uniprot
P29353 (SHC1) S54 Uniprot
P29353 (SHC1) T56 Uniprot
P29353 (SHC1) T386 Uniprot
P30279 (CCND2) T280 Uniprot
P30305 (CDC25B) S323 Uniprot
P30305 (CDC25B) S375 Uniprot
P30307 (CDC25C) S216 Uniprot
P31645 (SLC6A4) T616 Uniprot
P35236 (PTPN7) T66 Uniprot
P35236 (PTPN7) S93 Uniprot
P35236-2 (PTPN7) T105 Uniprot
P35236-2 (PTPN7) S132 Uniprot
P35638-1 (DDIT3) S79 Uniprot
P35638-1 (DDIT3) S82 Uniprot
P36956-3 (SREBF1) S39 Uniprot
P36956 (SREBF1) S63 Uniprot
P36956-3 (SREBF1) T402 Uniprot
P36956 (SREBF1) T426 Uniprot
P38936 (CDKN1A) T57 Uniprot
P38936 (CDKN1A) S130 Uniprot
P40763 (STAT3) S727 Uniprot
P41212 (ETV6) S22 Uniprot
P41212 (ETV6) S257 Uniprot
P41235-5 (HNF4A) S145 Uniprot
P41235 (HNF4A) S167 Uniprot
P41970 (ELK3) S357 Uniprot
P41970 (ELK3) S363 Uniprot
P42224 (STAT1) S727 Uniprot
P42566 (EPS15) S796 Uniprot
P42574 (CASP3) S150 Uniprot
P42677 (RPS27) S27 Uniprot
P47712 (PLA2G4A) S505 Uniprot
P49023 (PXN) S85 Uniprot
P49137-2 (MAPKAPK2) T25 Uniprot
P49137-2 (MAPKAPK2) T206 Uniprot
P49137-2 (MAPKAPK2) T222 Uniprot
P49137 (MAPKAPK2) S272 Uniprot
P49137-1 (MAPKAPK2) T317 Uniprot
P49137-1 (MAPKAPK2) T334 Uniprot
P49841 (GSK3B) S389 Uniprot
P49841 (GSK3B) T390 Uniprot
P49918 (CDKN1C) S146 Uniprot
P52945 (PDX1) S61 Uniprot
P52945 (PDX1) S66 Uniprot
P53667 (LIMK1) S310 Uniprot
P56178 (DLX5) S34 Uniprot
P56178 (DLX5) S217 Uniprot
P61244-2 (MAX) S40 Uniprot
P61244-6 (MAX) S49 Uniprot
P61244-2 (MAX) S135 Uniprot
P61244-1 (MAX) S144 Uniprot
P68431 (HIST1H3J) S11 Uniprot
P68431 (HIST1H3J) S29 Uniprot
P78356 (PIP4K2B) S326 Uniprot
P78536 (ADAM17) T735 Uniprot
P78543 (BTG2) S149 Uniprot
P84022 (SMAD3) S204 Uniprot
P84022 (SMAD3) S208 Uniprot
P84022-1 (SMAD3) S213 Uniprot
Q01844 (EWSR1) T79 Uniprot
Q02078 (MEF2A) S98 Uniprot
Q02078 (MEF2A) T108 Uniprot
Q02078 (MEF2A) S192 Uniprot
Q02078 (MEF2A) S223 Uniprot
Q02078-5 (MEF2A) T304 Uniprot
Q02078-5 (MEF2A) T311 Uniprot
Q02078 (MEF2A) T312 Uniprot
Q02078 (MEF2A) T319 Uniprot
Q02078 (MEF2A) S355 Uniprot
Q02078 (MEF2A) S408 Uniprot
Q02078-5 (MEF2A) S445 Uniprot
Q02078 (MEF2A) S453 Uniprot
Q02078 (MEF2A) S479 Uniprot
Q02078 (MEF2A) S494 Uniprot
Q02156 (PRKCE) S350 Uniprot
Q06330 (RBPJ) T339 Uniprot
Q06413 (MEF2C) T293 Uniprot
Q06413 (MEF2C) T300 Uniprot
Q06413 (MEF2C) S387 Uniprot
Q07666 (KHDRBS1) S58 Uniprot
Q07666 (KHDRBS1) T84 Uniprot
Q07817 (BCL2L1) S62 Uniprot
Q12778 (FOXO1) S416 Uniprot
Q12778 (FOXO1) S432 Uniprot
Q12778 (FOXO1) S470 Uniprot
Q12778 (FOXO1) T478 Uniprot
Q12778 (FOXO1) T560 Uniprot
Q13541 (EIF4EBP1) T37 Uniprot
Q13541 (EIF4EBP1) T46 Uniprot
Q13541 (EIF4EBP1) S65 Uniprot
Q13541 (EIF4EBP1) T70 Uniprot
Q14721 (KCNB1) S805 Uniprot
Q14765 (STAT4) S721 Uniprot
Q14790 (CASP8) S347 Uniprot
Q14934 (NFATC4) S168 Uniprot
Q14934 (NFATC4) S170 Uniprot
Q15046 (KARS) T52 Uniprot
Q15075 (EEA1) T1392 Uniprot
Q15596 (NCOA2) S736 Uniprot
Q15672 (TWIST1) S68 Uniprot
Q15717 (ELAVL1) T118 Uniprot
Q15750 (TAB1) S423 Uniprot
Q15750 (TAB1) T431 Uniprot
Q15750 (TAB1) S438 Uniprot
Q15750 (TAB1) S452 Uniprot
Q15750 (TAB1) S453 Uniprot
Q15750 (TAB1) S456 Uniprot
Q15750 (TAB1) S457 Uniprot
Q15910 (EZH2) T367 Uniprot
Q16539 (MAPK14) T180 Uniprot
Q16539 (MAPK14) Y182 Uniprot
Q86UR1 (NOXA1) S239 Uniprot
Q86UR1 (NOXA1) S282 Uniprot
Q8IW41-1 (MAPKAPK5) T182 Uniprot
Q8NHW3 (MAFA) S14 Uniprot
Q8NHW3 (MAFA) T57 Uniprot
Q8NHW3 (MAFA) T134 Uniprot
Q8TDD2 (SP7) S76 Uniprot
Q8TDD2 (SP7) S80 Uniprot
Q8WYK2-1 (JDP2) T148 Uniprot
Q92945 (KHSRP) T692 Uniprot
Q92993-2 (KAT5) T106 Uniprot
Q92993 (KAT5) T158 Uniprot
Q99460 (PSMD1) T273 Uniprot
Q99626 (CDX2) S283 Uniprot
Q99626 (CDX2) S287 Uniprot
Q99626 (CDX2) S291 Uniprot
Q99626 (CDX2) S295 Uniprot
Q9BR76 (CORO1B) S2 Uniprot
Q9BUB5-2 (MKNK1) T209 Uniprot
Q9BUB5-2 (MKNK1) T214 Uniprot
Q9BUB5 (MKNK1) T250 Uniprot
Q9BUB5 (MKNK1) T255 Uniprot
Q9H1K0 (RBSN) S215 Uniprot
Q9NQU5 (PAK6) S165 Uniprot
Q9NRR4 (DROSHA) S221 Uniprot
Q9NRR4 (DROSHA) S255 Uniprot
Q9NRR4 (DROSHA) T274 Uniprot
Q9NRR4 (DROSHA) S300 Uniprot
Q9NRR4 (DROSHA) S355 Uniprot
Q9UBK2-1 (PPARGC1A) T263 Uniprot
Q9UBK2 (PPARGC1A) S266 Uniprot
Q9UBK2 (PPARGC1A) T299 Uniprot
Q9UIG0 (BAZ1B) S158 Uniprot
Q9UL54-2 (TAOK2) S1031 Uniprot
Q9UQD0 (SCN8A) S553 Uniprot
Q9Y5Y9 (SCN10A) S552 Uniprot
Q9Y698 (CACNG2) T321 Uniprot
Q9Y6Q9 (NCOA3) T24 Uniprot
Q9Y6Q9 (NCOA3) S505 Uniprot
Q9Y6Q9-1 (NCOA3) S543 Uniprot
Q9Y6Q9 (NCOA3) S860 Uniprot
Q9Y6Q9-5 (NCOA3) S867 Uniprot

Research Backgrounds

Function:

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.

(Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minute and is inhibited by kinase-specific inhibitors SB203580 and siRNA.

PTMs:

Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory citokines, environmental stress or growth factors, which activates the enzyme. Dual phosphorylation can also be mediated by TAB1-mediated autophosphorylation. TCR engagement in T-cells also leads to Tyr-323 phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16. PPM1D also mediates dephosphorylation and inactivation of MAPK14.

Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation at Lys-53 increases the affinity for ATP and enhances kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3.

Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway.

Subcellular Location:

Cytoplasm. Nucleus.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Brain, heart, placenta, pancreas and skeletal muscle. Expressed to a lesser extent in lung, liver and kidney.

Subunit Structure:

Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK. Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation (By similarity). Interacts with SPAG9 and GADD45A (By similarity). Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60, SUPT20H and TAB1. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B. Interacts with PPM1D. Interacts with CDK5RAP3; recruits PPM1D to MAPK14 and may regulate its dephosphorylation.

Family&Domains:

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Research Fields

· Cellular Processes > Cell growth and death > Cellular senescence.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Signaling pathways regulating pluripotency of stem cells.   (View pathway)

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Rap1 signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Sphingolipid signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > TNF signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.

· Human Diseases > Neurodegenerative diseases > Amyotrophic lateral sclerosis (ALS).

· Human Diseases > Infectious diseases: Bacterial > Epithelial cell signaling in Helicobacter pylori infection.

· Human Diseases > Infectious diseases: Bacterial > Shigellosis.

· Human Diseases > Infectious diseases: Bacterial > Salmonella infection.

· Human Diseases > Infectious diseases: Bacterial > Pertussis.

· Human Diseases > Infectious diseases: Parasitic > Leishmaniasis.

· Human Diseases > Infectious diseases: Parasitic > Chagas disease (American trypanosomiasis).

· Human Diseases > Infectious diseases: Parasitic > Toxoplasmosis.

· Human Diseases > Infectious diseases: Bacterial > Tuberculosis.

· Human Diseases > Infectious diseases: Viral > Hepatitis C.

· Human Diseases > Infectious diseases: Viral > Influenza A.

· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

· Organismal Systems > Circulatory system > Adrenergic signaling in cardiomyocytes.   (View pathway)

· Organismal Systems > Development > Osteoclast differentiation.   (View pathway)

· Organismal Systems > Immune system > Platelet activation.   (View pathway)

· Organismal Systems > Immune system > Toll-like receptor signaling pathway.   (View pathway)

· Organismal Systems > Immune system > NOD-like receptor signaling pathway.   (View pathway)

· Organismal Systems > Immune system > RIG-I-like receptor signaling pathway.   (View pathway)

· Organismal Systems > Immune system > IL-17 signaling pathway.   (View pathway)

· Organismal Systems > Immune system > Th1 and Th2 cell differentiation.   (View pathway)

· Organismal Systems > Immune system > Th17 cell differentiation.   (View pathway)

· Organismal Systems > Immune system > T cell receptor signaling pathway.   (View pathway)

· Organismal Systems > Immune system > Fc epsilon RI signaling pathway.   (View pathway)

· Organismal Systems > Immune system > Leukocyte transendothelial migration.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

· Organismal Systems > Nervous system > Retrograde endocannabinoid signaling.   (View pathway)

· Organismal Systems > Nervous system > Dopaminergic synapse.

· Organismal Systems > Sensory system > Inflammatory mediator regulation of TRP channels.   (View pathway)

· Organismal Systems > Endocrine system > Progesterone-mediated oocyte maturation.

· Organismal Systems > Endocrine system > Prolactin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Relaxin signaling pathway.

References

1). Li X et al. Cyanidin-3-O-glucoside restores spermatogenic dysfunction in cadmium-exposed pubertal mice via histone ubiquitination and mitigating oxidative damage. J Hazard Mater 2019 Nov 17:121706 (PubMed: 31796358) [IF=9.038]

Application: WB    Species: Mice    Sample: testis

Figure 8 The representative photographs and grayscale analysis of proteins in testis from mice treated for 30 days involved in MAPK signaling pathway. (A) JNK and p-JNK. (B) ERK and p-ERK. (C) p38 and p-p38. Comparison between all groups was evaluated through One-way ANOVA. Mean±SD. n=4. **p<0.01, *p<0.05, compared with control group. ##p<0.01, #p<0.05, compared with Cd group. ns, not significant.

2). Zhou B et al. Hepatoma cell-intrinsic TLR9 activation induces immune escape through PD-L1 upregulation in hepatocellular carcinoma. Theranostics 2020 May 17;10(14):6530-6543. (PubMed: 32483468) [IF=8.579]

3). Duan R et al. A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus. J Clin Immunol 2019 Oct 17 (PubMed: 31625129) [IF=6.780]

Application: WB    Species: human    Sample: T cells

Fig. 2| Impaired ubiquitin editing function of mutant A20 activated NFκB and MAPK pathway.c NF-κB and MAPK pathways were activated in stimulated patient-derived T cells. Patient-derived T cells were stimulated with TNF-α (50 ng/ml). Whole cell lysates were immunoblotted with respective target proteins. Healthy parents from the pedigree served as healthy controls

4). Tao Y et al. LncRNA CD27-AS1 promotes acute myeloid leukemia progression through the miR-224-5p/PBX3 signaling circuit. Cell Death Dis 2021 May 18;12(6):510. (PubMed: 34006845) [IF=6.304]

Application: WB    Species: Human    Sample: AML cells

Fig. 5 CD27-AS1 regulates MAPK signaling pathway in the AML cell lines. a HL-60 and KG-1 cells were infected with LV-CD27-AS1 and LV-CD27- AS1-Sh1. Protein levels of P38, p-P38, JNK, p-JNK, p-C-raf, p-MEK1/2, ERK, and p-ERK were detected using western blotting. b Densitometry analysis of protein levels in both cells was performed. c U0126, a MEK1/2 inhibitor, was used to treat the AML cells with CD27-AS1 upregulation. Relative protein levels of p-ERK and ERK were measured using western blotting. d CCK-8 assay was performed to check cell viability. N = 3. Data were shown as means ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001.

5). Jia C et al. IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway. Cell Death Dis 2021 Jun 3;12(6):575. (PubMed: 34083516) [IF=6.304]

Application: WB    Species: Mouse    Sample: endothelial cells

Fig. 5 IL-37b inhibited the activation of ERK and NFκB in KD-treated ECs related to IL-1R8. a Effects of IL-37b treatment on the phosphorylation of ERK, JNK, p38, and NFκB p65 were assessed in the treated endothelial cells. b–e Quantitative analysis of these above proteins was conducted. Data are presented as mean ± SD (n = 3). Significance: *P < 0.05 vs. the HC group, and #P < 0.05 vs. the KD group. f, g Effects of IL-1R8 silencing on the activation of ERK and NFκB p65 were observed. Significance: *P < 0.05 vs. the HC group, #P < 0.05 vs. the KD group, and &P < 0.05 vs. the KD + IL-37b group. i The nuclear translocation of NFκB p65 was observed after silencing IL-1R8 expression (n = 3). Magnification: ×200, Scale bar = 100 μm. Experiments were done at least three times in triplicate.

6). Bian M et al. Halo and Pseudohalo Gold(I)-NHC Complexes Derived from 4,5-Diarylimidazoles with Excellent in Vitro and in Vivo Anticancer Activity Against HCC. J Med Chem 2020 Aug 3. (PubMed: 32787098) [IF=6.205]

7). Li C et al. FOXO1 mediates hypoxia-induced G0/G1 arrest in ovarian somatic granulosa cells via activating the TP53INP1-p53-CDKN1A pathway. Development 2021 Jun 21;dev.199453. (PubMed: 34152408) [IF=5.611]

8). Xia Z et al. The synthesis and bioactivity of pyrrolo[2,3-d]pyrimidine derivatives as tyrosine kinase inhibitors for NSCLC cells with EGFR mutations. Eur J Med Chem 2021 Nov 15;224:113711. (PubMed: 34315040) [IF=5.572]

9). Hou S et al. Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis. Eur J Med Chem 2021 Feb 5;211:113114. (PubMed: 33360793) [IF=5.572]

Application: WB    Species: mouse    Sample: colon

Fig. 6.| Inhibitory effect of compounds 19 and 6 on activated ASK1-p38/JNK signaling and up-regulated inflammatory cytokines in colon tissues of DSS-induced UC mice. (A)Western blot analysis of the protein levels of ASK1-MKK3/6-p38 and ASK1-MKK4/7-JNK signaling pathways as well as corresponding phosphorylated proteins. GAPDH was used as the loading control protein.

Application: WB    Species: mice    Sample: colon tissues

Fig. 6. Inhibitory effect of compounds 19 and 6 on activated ASK1-p38/JNK signaling and up-regulated inflammatory cytokines in colon tissues of DSS-induced UC mice. (A) Western blot analysis of the protein levels of ASK1-MKK3/6-p38 and ASK1-MKK4/7-JNK signaling pathways as well as corresponding phosphorylated proteins. GAPDH was used as the loading control protein. (B) Quantitative analysis of the ratios of phosphorylated proteins normalized to their unphosphorylated form. (C) The levels of inflammatory cytokines IL-1b, IL-6, TNF-a were detected using ELISA kits. Data are expressed as mean ± SEM (n ¼ 5e6 per group). Compared with the control group: # P < 0.05, ## P < 0.01, ### P < 0.001; Compared with the DSS þ Veh group: * P < 0.05, ** P < 0.01, *** P < 0.001.

10). Hou S et al. Design, synthesis and biological evaluation of 1H-indazole derivatives as novel ASK1 inhibitors. Eur J Med Chem 2021 Aug 5;220:113482. (PubMed: 33906048) [IF=5.572]

Application: WB    Species: human    Sample: HT-29 cells

Fig. 6. |Compounds 15 and 2 inhibited TNF-a-induced activation of the ASK1-p38/JNK signaling pathways. (A) Western blot analyses of ASK1, p38, JNK and the corresponding phosphorylation. b-actin was used as a loading control. (B) Quantification of the ratios of p-ASK1, p-p38, and p-JNK normalized to their corresponding unphosphorylated forms. Data were expressed as the mean ± SEM, n ¼ 3. Compared with the control þ Veh group, ##p < 0.01; compared with the TNF-a þ Veh group, *p < 0.05, **p < 0.01.

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