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Mitogen-activated protein kinase kinase 4

MKK4, SEK1, JNK kinase
This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK3. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: JNK, AP-1, p38, MAPK, ERK
Papers using MKK4 antibodies
Interleukin-1 (IL-1)-induced TAK1-dependent versus MEKK3-dependent NFκB activation pathways bifurcate at IL-1-receptor associated kinase modification
Ramji Dipak P. et al., In The International Journal of Biochemistry & Cell Biology, 2006
... The non-radioactive JNK kinase assay kit was from Cell Signalling Technology whereas small interfering RNA (siRNA) were from either Qiagen [p50 NF-κB (SI02654932); p65 ...
Papers on MKK4
AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia.
Young et al., New Haven, United States. In J Mol Cell Cardiol, 30 Jan 2016
Mitochondria isolated from KD hearts during reperfusion had intact membrane integrity, but demonstrated reduced oxidative capacity, increased hydrogen peroxide production and decreased resistance to mitochondrial permeability transition pore opening compared to WT. KD hearts showed increased activation of the mitogen activated protein kinase kinase 4 (MKK4) and downstream c-Jun terminal kinase (JNK) and greater necrosis during reperfusion after coronary occlusion.
HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells.
Yuan et al., Guangzhou, China. In Oncotarget, 30 Jan 2016
Knockdown of MKK7 but not MKK4 remarkably decreased JNK/c-Jun activity and proliferation, whereas ectopic MKK7-JNK1 reversed HDACI-induced c-Jun suppression.
Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats.
Kilarkaje et al., Kuwait, Kuwait. In Toxicol Appl Pharmacol, 15 Jan 2016
Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups.
Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway.
Huang et al., Wuhan, China. In Toxicol Appl Pharmacol, 15 Jan 2016
Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling.
Injury-induced rapid activation of MAPK signaling in dechorionated eggs and larvae of the silkworm, Bombyx mori.
Chen et al., Jieyang, China. In Insect Sci, 01 Jan 2016
A kinase assay showed a dramatic increase in JNK kinase activity in egg lysates upon injury.
SL4, a chalcone-based compound, induces apoptosis in human cancer cells by activation of the ROS/MAPK signalling pathway.
Wu et al., Shenyang, China. In Cell Prolif, 31 Dec 2015
SP600125 and SB203580, specific inhibitors of JNK kinase and p38 kinase, significantly retarded apoptosis induced by SL4.
Toll-like receptor 4 signaling promotes invasion of hepatocellular carcinoma cells through MKK4/JNK pathway.
Chen et al., Hangzhou, China. In Mol Immunol, 31 Dec 2015
LPS treatment dramatically increased the TLR4 expression on HCC cells surface and MKK4/JNK activation, while knockdown of TLR4 inhibited the LPS-induced invasion and the phosphorylation of MKK4 and JNK.
Mitogen-Activated Protein Kinase Kinase 4 Gene Polymorphism and Cancer Risk.
Liang et al., Chongqing, China. In Medicine (baltimore), Nov 2015
A number of epidemiological studies have assessed the association of -1304T > G polymorphism in the MKK4 gene and risk of cancer, but the results lack of statistical power due to the limited subjects used in these studies.
HMGB1 promotes HCC progression partly by downregulating p21 via ERK/c-Myc pathway and upregulating MMP-2.
Jiang et al., Shanghai, China. In Tumour Biol, Nov 2015
Molecular mechanism investigation revealed that knockdown HMGB1 significantly reduced the activation of MAPKs, including ERK1/2, p38, SAPK/JNK, as well as MAPKKs (MEK1/2, SEK1) and its substrates (c-Jun, c-Myc); downregulated NF-κB/p65 expression and phosphorylation level; decreased MMP-2 expression and activity; and upregulated p21 expression.
Pathological axonal death through a MAPK cascade that triggers a local energy deficit.
Tessier-Lavigne et al., New York City, United States. In Cell, Feb 2015
Further, MKK4, a key component in the Sarm1-MAPK pathway, is antagonized by AKT signaling, which modulates the degenerative response by limiting activation of downstream JNK signaling.
CIP2A overexpression induces autoimmune response and enhances JNK signaling pathway in human lung cancer.
Zhang et al., El Paso, United States. In Bmc Cancer, 2014
Furthermore, the expression level of CIP2A also affected the phosphorylation of the upstream kinase of JNK, MKK4/MKK7.
Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors.
Franzoso et al., Napoli, Italy. In Cancer Cell, 2014
Here, we identify the interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM.
Vulnerability of glioblastoma cells to catastrophic vacuolization and death induced by a small molecule.
Ernfors et al., Stockholm, Sweden. In Cell, 2014
The MAP kinase MKK4, identified by a shRNA screen, represents a critical signaling node.
A Direct in vivo RNAi screen identifies MKK4 as a key regulator of liver regeneration.
Zender et al., Hannover, Germany. In Cell, 2013
Our studies identify the dual-specific kinase MKK4 as a master regulator of liver regeneration.
Delayed cell cycle progression in selenoprotein W-depleted cells is regulated by a mitogen-activated protein kinase kinase 4-p38/c-Jun NH2-terminal kinase-p53 pathway.
Alkan et al., Davis, United States. In J Biol Chem, 2012
SEPW1 silencing increases MKK4, which activates p38gamma, p38delta, and JNK2 to phosphorylate p53 on Ser-33 and cause a transient G(1) arrest.
MAPK7 and MAP2K4 as prognostic markers in osteosarcoma.
Toledo et al., São Paulo, Brazil. In Hum Pathol, 2012
Overexpression of MAP2K4 in osteosarcoma was correlated with poor treatment response, disease progression and poor overall survival.
The association between -1304T>G polymorphism in the promoter of mitogen-activated protein kinase kinase 4 gene and the risk of cervical cancer in Chinese population.
Li et al., Suzhou, China. In Dna Cell Biol, 2012
the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of cervical cancer
Biological and prognostic relevance of mitogen-activated protein kinases in pancreatic adenocarcinoma.
Couvelard et al., Bobigny, France. In Pancreas, 2012
Suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation.
Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway.
Wang et al., Stanford, United States. In Nature, 2012
Complementary in vitro and in vivo assays show that BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4, and that activities of downstream MAPKs are reduced in brassinosteroid-deficient mutants but increased by treatment with either brassinosteroid or GSK3-kinase inhibitor.
Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation.
Xia et al., Cincinnati, United States. In J Biol Chem, 2012
Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation.
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