Product Name	MEK4
Chinese Name	丝裂原活化蛋白激酶激酶4抗体
Alias	c Jun N terminal kinase kinase 1; 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; Dual specificity mitogen-activated protein kinase kinase 4; JNK activated kinase 1; JNK Activated Kinase 1; JNK activating kinase 1; JNK activating kinase 1; JNK-activating kinase 1; JNKK 1; JNKK; JNKK; JNKK-1; JNKK-1; JNKK1; JNKK1; MAP kinase kinase 4; MAP kinase kinase 4; MAP2K4; MAPK / ERK kinase 4; MAPK / ERK kinase 4; MAPK ERK kinase 4; MAPK/ERK kinase 4; MAPKK 4; MAPKK 4; MAPKK-4; MAPKK-4; MAPKK4; MAPKK4; MEK 4; MEK 4; MEK-4; MEK-4; MEK4; Mitogen Activated Protein Kinase Kinase 4; MKK 4; MKK-4; MKK-4; MKK4; MP2K4_HUMAN; PRKMK 4; PRKMK 4; PRKMK-4; PRKMK-4; PRKMK4; PRKMK4; SAPK / ERK kinase 1; SAPK / ERK kinase 1; SAPK ERK kinase 1; SAPK/ERK Kinase 1; SEK 1; SEK1; SEK1; SERK 1; SERK-1; SERK-1; SERK1; SERK1.
Research Area	Tumour  Cell biology  immunology  Signal transduction  transcriptional regulatory factor  Kinases and Phosphatases
Immunogen Species	Rabbit
Clonality	Polyclonal
React Species	(predicted: Human, Mouse, Rat, Dog, Cow, )
Applications	ELISA=1:5000-10000 IHC-P=1:100-500 IHC-F=1:100-500 IF=1:100-500 （Paraffin sections need antigen repair） not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user.
Theoretical molecular weight	44kDa
Cellular localization	The nucleus
Form	Liquid
Concentration	1mg/ml
immunogen	KLH conjugated synthetic peptide derived from human MKK4/MAP2K4: 301-399/399
Lsotype	IgG
Purification	affinity purified by Protein A
Buffer Solution	0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol.
Storage	Shipped at 4℃. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles.
Attention	This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
PubMed	PubMed
Product Detail	This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family 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. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013] 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. Subunit: 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. Subcellular Location: Cytoplasm. Nucleus. Tissue Specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues. Post-translational modifications: Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks). Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain. SWISS: P45985 Gene ID: 6416 Database links: Entrez Gene: 6416 Human Entrez Gene: 26398 Mouse Omim: 601335 Human SwissProt: P45985 Human SwissProt: P47809 Mouse Unigene: 514681 Human Unigene: 412922 Mouse         研究发现---丝裂原活化蛋白激酶激酶4（MKK4）信号途径对肝脏再生具有重要的意义     肝脏是人体最大的内脏器官，承担着数百种功能，包括产生蛋白质与凝血因子，以及促进消化与能量释放等。肝功能衰竭（Liver Failure）是由于肝细胞受到广泛严重的损害，机体代谢功能发生严重紊乱而出现的临床综合征。肝衰竭发生于许多严重的肝脏疾病过程中，症候险恶，预后多不良。     近日，俄勒冈健康与科学大学，加州大学旧金山分校的研究人员介绍了近期一项可用于治疗肝功能衰竭的新成果：研究人员发现了著名信号途径JNK中的一种激酶——丝裂原活化蛋白激酶激酶4（MKK4）对肝脏再生具有重要的意义。相关文章刊登在了近期出版的《细胞》（Cell）杂志上。     研究显示肝细胞质量是通过肝细胞死亡和再生之间的平衡来维系的，急性和慢性肝功能损伤会失去这种再生能力。因此围绕肝脏再生，科学家们展开了许多研究。在这篇文章中，研究人员发现了一种潜在的药物靶标，能增强肝细胞增殖，促进肝脏再生，防止肝功能衰竭。     研究人员研发了一种能有效筛选动物疾病模型中调控肝脏再生基因的方法，他们在对小鼠肝脏中数百个基因的表达进行干扰分析后，发现在急性和慢性肝损伤后，抑制MKK4基因能有效增加肝细胞的生成和生存，从而促进肝脏修复，增加小鼠的寿命。而且这种MKK4基因的抑制，也会提高培养基中肝细胞长时间存活的数量，这为促进肝病患者肝移植提供了一种新方法。     研究人员表示，这一成果指出MKK4也许能作为一种促进肝细胞增殖，肝脏再生的药物靶标，这为研发新型肝病治疗方法提出了新思路。     此前，这组研究人员通过观察成体Stem cells标记物Lgr5，以及响应生长因子Wnt的细胞生长，第一次鉴别出了小肠和结肠中的Stem cells。并推测，Lgr5的独特表达模式也可以用于标记其他成体组织，包括肝脏中的Stem cells。并在这一方法的基础上进行了改良，利用新方法，研究人员发现Wnt诱导Lgr5表达不仅可以标记肝脏中的Stem cells生成，还可以确定一种在肝损伤时变得活跃的Stem cells。     研究人员希望能大规模的扩增这些肝细胞，随后将它们转化为肝细胞，用于治疗人类慢性肝病。

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