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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
Supplier
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
Synergistic Toxic Interactions Between CYP2E1, LPS/TNFα, and JNK/p38 MAP Kinase and Their Implications in Alcohol-Induced Liver Injury.
New
Wu et al., New York City, United States. In Adv Exp Med Biol, 31 Dec 2014
This activation of ASK-1 is followed by activation of the mitogen-activated kinase kinases MKK3/MKK6 and MKK4/MMK7 and subsequently p38 and JNK MAP kinases.
Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma.
New
Sayar et al., Ankara, Turkey. In Int J Dermatol, 27 Dec 2014
Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs.
Genistein alleviates pressure overload-induced cardiac dysfunction and interstitial fibrosis in mice.
New
Du et al., Key West, United States. In Br J Pharmacol, 03 Dec 2014
Gen suppressed TAK1 expression and produced anti-fibrotic effects by blocking the TAK1/MKK4/JNK pathway.
Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors.
New
Impact
Franzoso et al., Napoli, Italy. In Cancer Cell, 13 Nov 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.
New
Impact
Ernfors et al., Stockholm, Sweden. In Cell, May 2014
The MAP kinase MKK4, identified by a shRNA screen, represents a critical signaling node.
The Daidzein Metabolite, 6,7,4'-Trihydroxyisoflavone, Is a Novel Inhibitor of PKCα in Suppressing Solar UV-Induced Matrix Metalloproteinase 1.
New
Lee et al., Seoul, South Korea. In Int J Mol Sci, Dec 2013
The mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MKK)3/6/p38 and MKK4/c-Jun N-terminal kinases (JNK) signaling pathways are known to modulate MMP-1 function, and their activation by sUV was significantly reduced by 6,7,4'-THIF pretreatment.
Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and their therapeutic potential.
Review
New
Liu et al., Sacramento, United States. In Transl Stroke Res, Dec 2013
In the brain, protein kinase D phosphorylates Hsp27 following ischemia which then binds apoptosis signal-regulating kinase 1 to prevent MKK4/7, c-Jun NH(2)-terminal kinase, and Jun-induced apoptosis, and decrease infarct volumes following focal cerebral ischemia.
A Direct in vivo RNAi screen identifies MKK4 as a key regulator of liver regeneration.
New
Impact
Zender et al., Hannover, Germany. In Cell, May 2013
Our studies identify the dual-specific kinase MKK4 as a master regulator of liver regeneration.
[Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy].
Review
Mielicki et al., In Postepy Hig Med Dosw (online), 2012
It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins.
[Protein phosphatase MKP-1 participates in c-fos gene derepression under the action of stress factors on fibroblasts transformed with E1A and cHA-ras oncogenes].
In Tsitologiia, 2012
Use of inhibitors of MAP-kinase has revealed that MKP-1 gene transcription depends on MEK/ERK and JNK kinase cascades, but not om p38 cascade.
Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents.
Review
Sang et al., Tallahassee, United States. In Med Res Rev, 2012
CD44s is decreased in both PIN and cancer; Drg-1, E-cadherin, KAI-1, RKIP, and SSeCKS show similar expression between benign epithelia and PIN, but are downregulated in invasive cancer; whereas, maspin, MKK4, Nm23 and PTEN are upregulated in PIN and downregulated in cancer.
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.
GeneRIF
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.
GeneRIF
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.
GeneRIF
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
Role of ion transport in control of apoptotic cell death.
Review
Hoffmann et al., Tübingen, Germany. In Compr Physiol, 2012
Signaling involved in the modification of cell-volume regulatory ion transport during apoptosis include mitogen-activated kinases p38, JNK, ERK1/2, MEKK1, MKK4, the small G proteins Cdc42, and/or Rac and the transcription factor p53. Osmosensing involves integrin receptors, focal adhesion kinases, and tyrosine kinase receptors.
Biological and prognostic relevance of mitogen-activated protein kinases in pancreatic adenocarcinoma.
GeneRIF
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.
Impact
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.
GeneRIF
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.
[Neuroprotective effect of ischemic postconditioning and remote preconditioning. Prospective of clinical use].
Review
Lishmanov et al., In Angiol Sosud Khir, 2011
It was established that foregoing effect of ischemic postconditioning depended upon an activation of PKCs, ERK, Akt kinases and a decrease in the activity of JNK kinase.
The ATAC acetyltransferase complex coordinates MAP kinases to regulate JNK target genes.
Impact
Workman et al., Kansas City, United States. In Cell, 2010
Under conditions of osmotic stress, ATAC colocalizes with c-Jun, recruits the upstream kinases Misshapen, MKK4, and JNK, and suppresses further activation of JNK.
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