Recombinant Mouse MKK4 Protein (His & GST Tag)

Beta LifeScience SKU/CAT #: BLPSN-3376

Recombinant Mouse MKK4 Protein (His & GST Tag)

Beta LifeScience SKU/CAT #: BLPSN-3376
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Product Overview

Tag His&GST
Host Species Mouse
Accession P47809
Synonym JNKK1, MEK4, MKK4, PRKMK4, Sek1, Serk1
Background Dual specificity mitogen-activated protein kinase kinase 4, also known as MAP kinase kinase 4, MAPKK4, JNK-activating kinase 1, MAPK/ERK kinase 4, SAPK/ERK kinase 1, c-Jun N-terminal kinase kinase 1, JNKK and MAP2K4, is a protein which belongs to theprotein kinase superfamily, STE Ser/Thr protein kinase family and MAP kinase kinase subfamily. MAP2K4 / JNKK1 is a protein kinase which is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. MAP2K4 / JNKK1 has been shown to activate MAPK8 / JNK1, MAPK9 / JNK2, and MAPK14 / p38, but not MAPK1 / ERK2 or MAPK3 / ERK1. MAP2K4 / JNKK1 is phosphorylated, and thus activated by MAP3K1 / MEKK. The stress-activated protein kinase (SAPK) pathways represent phosphorylation cascades that convey pro-apoptotic signals. The mitogen-activated protein kinase kinase (MAPKK) homolog MAP2K4 ( MKK4, SEK, JNKK1 ) is a centrally-placed mediator of the SAPK pathways.
Description A DNA sequence encoding the mouse MAP2K4 (P47809) (Ala 2-Asp 397) was fused with the N-terminal His-tagged GST tag at the N-terminus.
Source Baculovirus-Insect Cells
Predicted N Terminal Met
AA Sequence Ala 2-Asp 397
Molecular Weight The secreted recombinant mouse MAP2K4/GST chimera consists of 633 a.a. and has a calculated molecular mass of 72 kDa. The recombinant protein migrates as an approximately 65 kDa band in SDS-PAGE under reducing conditions.
Purity >90% as determined by SDS-PAGE
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Formulation Lyophilized from sterile 20mM Tris, 500mM NaCl, pH 8.5.
Stability The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage For Research Use Only
Storage Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target 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.
Subcellular Location Cytoplasm. Nucleus.
Protein Families Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily
Database References
Tissue Specificity Strong expression is detected in most of the central nervous system and in liver and thymus during early stages of development. While expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenes

Gene Functions References

  1. MKK4 is the major MAP2K, which activates JNK in acute liver injury. p38, the other downstream target of MKK4, does not contribute to liver injury from APAP or TNF/galactosamine. PMID: 28661486
  2. MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing. PMID: 28733031
  3. This study provides compelling evidence for the pivotal roles of the ZPK/DLK and MKK4/MAP2K4-dependent mechanism in axotomy-induced motoneuron death in neonates. PMID: 25100604
  4. The loss of mkk4 and mkk7 locks damaged exocrine cells in a permanently de-differentiated state. PMID: 24713432
  5. Studies identify the dual-specific kinase MKK4 as a master regulator of liver regeneration. MKK4 silencing robustly increased the regenerative capacity of hepatocytes in mouse models of liver regeneration and acute and chronic liver failure. PMID: 23582328
  6. Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation. PMID: 22130668
  7. MKK4/7 and JNK1/2 played regulatory role in cytoskeleton reorganization during vaccinia virus infection. PMID: 22031940
  8. These data support a model in which MKK4 activation at the metastatic site causes a cell-cycle arrest. PMID: 21351092
  9. Mitogen-activated protein kinase kinase 4 deficiency in cardiomyocytes causes connexin 43 reduction and couples hypertrophic signals to ventricular arrhythmogenesis. PMID: 21454599
  10. 7,3',4'-Trihydroxyisoflavone, a metabolite of the soy isoflavone daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4 PMID: 21378167
  11. Results provide the first genetic demonstration that MKK4 is essential to mediate the oncogenic effect of Ras in vivo. PMID: 20610622
  12. Enhancement of erythropoietin-stimulated cell proliferation by Anandamide correlates with increased activation of the mitogen-activated protein kinases ERK1 and ERK2. PMID: 11920199
  13. Jun N-terminal kinase has a role in IL-4 induction PMID: 12368275
  14. SEK1 appears to play a crucial role in hepatoblast proliferation and survival in a manner apparently different from NF-kappaB or c-Jun. PMID: 12376107
  15. MKK4 is one of three protein kinases which activate p38 MAPK in vitro. PMID: 12893778
  16. Disruption of MKK4 signaling reveals its tumor suppressor role in embryonic stem cells. PMID: 15122334
  17. MKK4 promotes cell survival by activating phosphatidylinositol 3-kinase through an NF kappa B/PTEN-dependent pathway. PMID: 17158870
  18. Differential employment of MKK4 and MKK7 by scaffold proteins Axin, Dvl, and Epstein-Barr virus latent membrane protein-1 (LMP-1) in mediating JNK activation was examined. PMID: 17187786
  19. the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract ROS accumulation, and when this pathway fails, excessive ROS leads to activation of the MKK4-JNK pathway, resulting in apoptosis PMID: 17526490
  20. SGK1 negatively regulates stress-activated signaling through inhibition of SEK1 function PMID: 17568772
  21. MKK4 plays a central role in tumor necrosis factor (TNF)-induced apoptosis through the regulation of NF-kappa B-regulated gene products. PMID: 17641059
  22. Data demonstrate that MKK4 is an essential activator of JNK required for the normal development of the brain. PMID: 17875933
  23. Knockdown of MKK4 attenuated the myostatin-induced downregulation of MyoD and myogenin expression. PMID: 18049864
  24. These results suggest that HSP70 expression is up-regulated by SEK1 and down-regulated by MKK7 through distinct MAPK isoforms in mouse embryonic stem cells treated with cadmium chloride. PMID: 18348256
  25. Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth. PMID: 19265040
  26. MKK4 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase Itch, which has a fundamental role in the mechanism that controls MKK4 protein levels. PMID: 19737936


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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

To learn more about how to properly dissolve the lyophilized recombinant protein, please visit Lyophilization FAQs.

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