Product: Phospho-MEK4/MKK4 (Ser80) Antibody
Catalog: AF3321
Description: Rabbit polyclonal antibody to Phospho-MEK4/MKK4 (Ser80)
Application: WB IHC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
Mol.Wt.: 44kDa; 44kD(Calculated).
Uniprot: P45985
RRID: AB_2834740

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 100ul $280 In stock
 200ul $350 In stock

Lead Time: Same day delivery

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
Clonality:
Polyclonal
Specificity:
Phospho-MEK4/MKK4 (Ser80) Antibody detects endogenous levels of MEK4/MKK4 only when phosphorylated at Serine 80.
RRID:
AB_2834740
Cite Format: Affinity Biosciences Cat# AF3321, RRID:AB_2834740.
Conjugate:
Unconjugated.
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

c Jun N terminal kinase kinase 1; C-JUN N-terminal kinase kinase 1; Dual specificity mitogen activated protein kinase kinase 4; Dual specificity mitogen-activated protein kinase kinase 4; JNK Activated Kinase 1; JNK activating kinase 1; JNK-activating kinase 1; JNKK; JNKK1; MAP kinase kinase 4; Map2k4; MAPK ERK kinase 4; MAPK/ERK kinase 4; MAPKK 4; MAPKK4; MEK 4; MEK4; Mitogen activated protein kinase kinase 4; MKK 4; MKK4; MP2K4_HUMAN; PRKMK4; SAPK ERK kinase 1; SAPK/ERK kinase 1; SAPKK 1; SAPKK1; SEK1; SERK1; SKK1; Stress activated protein kinase kinase 1;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
P45985 MP2K4_HUMAN:

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Description:
MKK4 dual specificity kinase of the STE7 family that phosphorylates and activates JNK1 and -2 as well as p38 but not ERK1 or -2. Mediates cellular responses to various cellular stresses and inflammatory cytokines. Phosphorylation by Akt inhibits MKK4 and suppresses stress-activated signal transduction.
Sequence:
MAAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKALKLNFANPPFKSTARFTLNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPSSPMYVD

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
Xenopus
100
Chicken
100
Rabbit
100
Zebrafish
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P45985 As Substrate

Site PTM Type Enzyme
A2 Acetylation
S5 Phosphorylation
S7 Phosphorylation
S18 Phosphorylation
S26 Phosphorylation
K42 Methylation
K45 Methylation
K54 Methylation
T56 Phosphorylation
R58 Methylation
T78 Phosphorylation
S80 Phosphorylation O00141 (SGK1) , P31749 (AKT1)
S83 Phosphorylation
K86 Ubiquitination
K88 Ubiquitination
S90 Phosphorylation
K103 Ubiquitination
K131 Acetylation
K131 Ubiquitination
K140 Ubiquitination
K143 Ubiquitination
K214 Ubiquitination
K231 Ubiquitination
S257 Phosphorylation Q16584 (MAP3K11) , P45985 (MAP2K4)
T261 Phosphorylation Q02779 (MAP3K10) , Q16584 (MAP3K11) , Q13233 (MAP3K1) , P45985 (MAP2K4) , Q99683 (MAP3K5)
T391 Phosphorylation
S393 Phosphorylation
S394 Phosphorylation

PTMs - P45985 As Enzyme

Substrate Site Source
P04637 (TP53) S33 Uniprot
P19793 (RXRA) Y249 Uniprot
P45983 (MAPK8) T183 Uniprot
P45983 (MAPK8) Y185 Uniprot
P45983-3 (MAPK8) T228 Uniprot
P45983-3 (MAPK8) S284 Uniprot
P45983-3 (MAPK8) S377 Uniprot
P45984-1 (MAPK9) Y185 Uniprot
P45985 (MAP2K4) S257 Uniprot
P45985 (MAP2K4) T261 Uniprot
P53778 (MAPK12) T183 Uniprot
P53778 (MAPK12) Y185 Uniprot
P53779-3 (MAPK10) T183 Uniprot
P53779-3 (MAPK10) Y185 Uniprot
P53779-2 (MAPK10) T221 Uniprot
P53779 (MAPK10) Y223 Uniprot
Q16539 (MAPK14) T180 Uniprot
Q16539 (MAPK14) Y182 Uniprot

Research Backgrounds

Function:

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

PTMs:

Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).

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:

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Subunit Structure:

Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.

Family&Domains:

The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.

The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.

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

Research Fields

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

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

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

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

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

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

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

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

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

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

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

· Organismal Systems > Endocrine system > Relaxin signaling pathway.

References

1). Shi C et al. JNK signaling pathway mediates acetaminophen-induced hepatotoxicity accompanied by changes of glutathione S-transferase A1 content and expression. Frontiers in Pharmacology 2019 Sep 20;10:1092. (PubMed: 31620005) [IF=5.6]

Application: WB    Species: mouse    Sample: liver

FIGURE 2 | Activation of JNK signaling pathway under different dosages of APAP.(E) Western blot analyses of total tissue lysate for p-ASK1, ASK1, p-MKK4, MKK4, and β-actin (loading control). Values represented as means ± SD, n = 3. *Represents statistical differences caused by APAP. #Represents statistical differences caused by SP600125 under 150 mg·kg−1 APAP;§Represents statistical differences caused by SP600125 under 175 mg·kg−1 APAP. 0.05 > P > 0.01 (*, #, §). P < 0.01 (**, §§).

2). Liberation of daidzein by gut microbial b-galactosidase suppresses acetaminopheninduced hepatotoxicity in mice.

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