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These results provide valuable insights into the role of acetylation in MKK4-JNK signaling in T cells.
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.
MKK4 overexpression enhanced TNF-alpha-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation.
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.
Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression
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
MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing.
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.
These results suggest that ROCK may be important in IL-1-induced signaling through MKK4 to JNK and the activation of p38 MAPK.
Association between MKK4 promoter polymorphism and breast cancer risk in Kashmiri population
In Chinese Han ischemic stroke patients rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels.
the presence of the -1304T > G polymorphism is likely to decrease risk of cancer (Meta-Analysis)
The plasma level of protein MAP2K4 was found to suggestively associate negatively with the volume of the left entorhinal cortex in asymptomatic older twins.
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.
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.
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.
knockdown of Sec8 enhances the binding of JIP4 to MAPK kinase 4, thereby decreasing the phosphorylation of MAPK kinase 4, JNK, and p38.
Demonstrate that Mkk4 is a negative regulator of the TGF-beta1 signaling associated with atrial remodeling and arrhythmogenesis with age.
MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells.
Lipopolysaccharide induced miR-181a promotes pancreatic cancer cell migration via targeting PTEN and MAP2K4.
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.
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.
The loss of mkk4 and mkk7 locks damaged exocrine cells in a permanently de-differentiated state.
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.
MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase
Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation.
MKK4/7 and JNK1/2 played regulatory role in cytoskeleton reorganization during vaccinia virus infection.
These data support a model in which MKK4 activation at the metastatic site causes a cell-cycle arrest.
Mitogen-activated protein kinase kinase 4 deficiency in cardiomyocytes causes connexin 43 reduction and couples hypertrophic signals to ventricular arrhythmogenesis.
7,3',4'-Trihydroxyisoflavone, a metabolite of the soy isoflavone daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4
Results provide the first genetic demonstration that MKK4 is essential to mediate the oncogenic effect of Ras in vivo.
Enhancement of erythropoietin-stimulated cell proliferation by Anandamide correlates with increased activation of the mitogen-activated protein kinases ERK1 and ERK2.
Jun N-terminal kinase has a role in IL-4 induction
SEK1 appears to play a crucial role in hepatoblast proliferation and survival in a manner apparently different from NF-kappaB or c-Jun.
MKK4 is one of three protein kinases which activate p38 MAPK in vitro.
Disruption of MKK4 signaling reveals its tumor suppressor role in embryonic stem cells.
MKK4 promotes cell survival by activating phosphatidylinositol 3-kinase through an NF kappa B/PTEN-dependent pathway.
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.
in Drosophila both MAPKKs, Hep/Mkk7 and Mkk4, are required to induce JNK upon TNF or pro-inflammatory stimulation
The Arabidopsis MKK4/MKK5-MPK6 cascade is an important player in the maternal control of embryogenesis.
MKK4, MKK5, MKK7, and MKK9, are responsible for the activation of MPK3 and MPK6 by melatonin, indicating that melatonin-mediated innate immunity is triggered by MAPK signaling through MKK4/5/7/9-MPK3/6 cascades.
our data indicate that EDR1 physically associates with MKK4/MKK5 and negatively regulates the MAPK cascade to fine-tune plant innate immunity.
Results suggest that the YDA-MKK4/MKK5-MPK3/MPK6 cascade functions downstream of the ER receptor in regulating localized cell proliferation, which further shapes the morphology of plant organs.
MKK4 is involved in the osmotic-stress response via its regulation of MPK3 activity.
MKK4 is a key regulator of stomatal development and patterning.
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.
JNK activating kinase 1
, JNK-activated kinase 1
, JNK-activating kinase 1
, MAP kinase kinase 4
, MAPK/ERK kinase 4
, MAPKK 4
, MEK 4
, SAPK/ERK kinase 1
, c-Jun N-terminal kinase kinase 1
, dual specificity mitogen-activated protein kinase kinase 4
, stress-activated protein kinase kinase 1
, C-JUN N-terminal kinase kinase 1
, JNK kinase 1
, JNKK 1
, SAPK/Erk/kinase 1
, mitogen activated protein kinase kinase 4, variant 1
, mitogen-activated protein kinase kinase 4
, JNK kinase 2
, Map kinase kinase 4
, drosophila MAP kinase kinase 4