Recombinant Human Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 (MAP2K4) Protein (His&Myc)

Name: Recombinant Human Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 (MAP2K4) Protein (His&Myc)
Brand: Beta LifeScience
SKU: BLC-07141P
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 (MAP2K4) Protein (His&Myc) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	P45985
Target Symbol	MAP2K4
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His&C-Myc
Target Protein Sequence	AAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKALKLNFANPPFKSTARFTLNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMVHKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYELATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATPSSPMYVD
Expression Range	2-399aa
Protein Length	Full Length of Mature Protein
Mol. Weight	51.6 kDa
Research Area	Signal Transduction
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

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	HGNC: 6844 OMIM: 601335 KEGG: hsa:6416 STRING: 9606.ENSP00000262445 UniGene: PMID: 29248490 This study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38 alpha, leading to a complex displaying significantly different dynamics across the bound regions. PMID: 29276882 MKK4 overexpression enhanced TNF-alpha-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation. PMID: 29072705 Study provides evidence that phosphorylated MKK4 (pMKK4) might function as a tumor suppressor in colorectal cancer (CRC). Downregulation of pMKK4 was associated with a more aggressive phenotype and with increases in local invasion and metastasis. pMKK4 was also strongly associated with disease-free survival. PMID: 28423721 Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression PMID: 27594411 the expression level of MAP2K4 was inversely associated with the expression of miR-802 in tongue squamous cell carcinoma (TSCC) tissues; demonstration that the MAP2K4 expression was upregulated in TSCC cell lines; elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression PMID: 28319306 MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing. PMID: 28733031 Manipulating the expression of both miR-222 and miR-25 influenced diverse gene expression changes in thyroid cells. Increased expression of miR-25 reduced MEK4 and TRAIL protein expression, and cell adhesion and apoptosis are important aspects of miR-25 functioning in thyroid cells. PMID: 27353001 Association between MKK4 promoter polymorphism and breast cancer risk in Kashmiri population PMID: 27509166 In Chinese Han ischemic stroke patients rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. PMID: 26856463 the presence of the -1304T > G polymorphism is likely to decrease risk of cancer (Meta-Analysis) PMID: 26554761 The plasma level of protein MAP2K4 was found to suggestively associate negatively with the volume of the left entorhinal cortex in asymptomatic older twins. PMID: 26080319 MAP2K4 increases human prostate cancer metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. PMID: 25019290 MKK4 is activated in vitro by reduced Trx but not oxidized Trx in the absence of an upstream kinase, suggesting that autophosphorylation of this protein occurs due to reduction of Cys-246 and Cys-266 by Trx. PMID: 26028649 Data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA. PMID: 25732927 knockdown of Sec8 enhances the binding of JIP4 to MAPK kinase 4, thereby decreasing the phosphorylation of MAPK kinase 4, JNK, and p38. PMID: 25244576 Demonstrate that Mkk4 is a negative regulator of the TGF-beta1 signaling associated with atrial remodeling and arrhythmogenesis with age. PMID: 24721794 MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. PMID: 24556602 Single nucleotide polymorphisms in MAP2K4 gene is associated with gastric cancer. PMID: 23921907 Arrestin-3 directly interacts with MKK7 and promotes JNK3alpha2 phosphorylation by both MKK4 and MKK7 in vitro as well as in intact cells. PMID: 23960075 If both p53 and the SAPKK MKK4 are simultaneously inactivated, persistent polo-like kinase 4 activity combined with the lack of SAPK-mediated inhibition of centrosome duplication conspire to induce supernumerary centrosomes under stress. PMID: 23653187 Rs12939944 located in the MAP2K4 intron was associated with decreased risk. PMID: 23299404 MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase PMID: 23355465 Crystal structures combined with small-angle X-ray scattering experiments revealed that the apo form of non-phosphorylated MAP2K4 (npMAP2K4) exists in a transient state which has a longer conformation compared with the typical kinase folding. PMID: 22828509 Results suggest that the functional -1304G variant in the MKK4 promoter decreases the risk of PCa by increasing the promoter activity. PMID: 22526163 the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of cervical cancer PMID: 22335172 Overexpression of MAP2K4 in osteosarcoma was correlated with poor treatment response, disease progression and poor overall survival. PMID: 22154052 Suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation. PMID: 22158075 protective role of genetic variant MKK4 -1304T>G is restrained in nasopharyngeal carcinoma (NPC) with Epstein-Barr Virus (EBV) infection. These findings implicate the role of EBV and MKK4 -1304 T>G interaction as a causative factor for the NPC. PMID: 21702039 MKK4 was identified as playing a key role in Tau-S422 phosphorylation in human neuroblastoma cells. PMID: 21638028 The purpose of the study was to investigate the potential contribution of HPK1, MEKK1, TAK1, p-MKK4 to the development of extramammary Paget disease PMID: 21915030 Building on the foundation of daring hypotheses: using the MKK4 metastasis suppressor to develop models of dormancy and metastatic colonization. PMID: 21925502 8 out of 11 cancer-associated MAP2K4 mutations reduce MKK4 protein stability or impair its kinase activity PMID: 21896780 MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort. PMID: 21575258 These results indicated that MKK4 acts as a tumor suppressor and may represent an important therapeutic target for the treatment of ovarian cancer PMID: 21487811 Compared with the -1304TT genotype, patients with the -1304TG genotype had a significantly decreased risk of acute myeloid leukemia PMID: 21518142 Loss of MKK4 expression is associated with endometrial cancer. PMID: 21372598 These results suggest that JNK affects the association of alpha-catenin with the adherens junction complex and regulates adherens junctions. PMID: 21030692 Data indicate that MKK4 gene knockdown in MDAH2774 cells over-expressing MKK4 increased invasion activity. PMID: 20309881 the crystal structures of human non-phosphorylated MKK4 kinase domain (npMKK4) complexed with AMP-PNP (npMKK4/AMP) and a ternary complex of npMKK4, AMP-PNP and p38alpha peptide (npMKK4/AMP/p38) were determined. PMID: 20732303 Functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity. PMID: 20554746 Elevated MKK4 abundance inhibited cell proliferation and increased the phosphorylation and activity of p38 and PRAK. Thus, multiple microRNAs acting on a single target, the MKK4 mRNA, collectively influence MKK4 abundance during replicative senescence PMID: 19861690 There appears to be consistent rate of genetic inactivation of MAP2K4 among most tumor types, including breast cancer. PMID: 11754110 JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage PMID: 12223490 Jun N-terminal kinase has a role in IL-4 induction PMID: 12368275 in the setting of wild-type PTEN, PI3K- and MKK4/JNK-dependent pathways cooperate to maintain cell survival. PMID: 12714585 regulation of fibroblast functions important for wound healing by basal JNK activity PMID: 12730213 docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates PMID: 12788955 JNK, MKK-4, and MKK-7 form an active signaling complex in rheumatoid arthritis and this novel JNK signalsome is activated in response to IL-1 and migrates to the nucleus PMID: 13130464 JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression PMID: 14511403

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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.

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