scholarly journals Production of Japanese Black calves by the transfer of embryos developed from in vitro-fertilized oocytes derived by ovum pick up and matured in culture with the mitogen-activated protein kinase kinase inhibitor U0126

2019 ◽  
Vol 81 (3) ◽  
pp. 379-382 ◽  
Author(s):  
Nobutada SAKAGAMI ◽  
Kunitoshi KONDA ◽  
Shinji HASHIMURA ◽  
Noritoshi KAWATE ◽  
Toshio INABA ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib inRAS-mutant relapsed or refractory myeloid malignancies

Cancer ◽  
2016 ◽  
Vol 122 (12) ◽  
pp. 1871-1879 ◽  
Author(s):  
Gautam Borthakur ◽  
Leslie Popplewell ◽  
Michael Boyiadzis ◽  
James Foran ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Myeloid Malignancies ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Phosphorylation of Argonaute 2 at serine-387 facilitates its localization to processing bodies

2008 ◽  
Vol 413 (3) ◽  
pp. 429-436 ◽  
Author(s):  
Yan Zeng ◽  
Heidi Sankala ◽  
Xiaoxiao Zhang ◽  
Paul R. Graves
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Kinase Inhibitor ◽  
Mapk Pathway ◽  
Phosphorylation Site ◽  
Mitogen Activated Protein Kinase ◽  
Processing Bodies ◽  
Mitogen Activated Protein

Ago (Argonaute) proteins are essential effectors of RNA-mediated gene silencing. To explore potential regulatory mechanisms for Ago proteins, we examined the phosphorylation of human Ago2. We identified serine-387 as the major Ago2 phosphorylation site in vivo. Phosphorylation of Ago2 at serine-387 was significantly induced by treatment with sodium arsenite or anisomycin, and arsenite-induced phosphorylation was inhibited by a p38 MAPK (mitogen-activated protein kinase) inhibitor, but not by inhibitors of JNK (c-Jun N-terminal kinase) or MEK [MAPK/ERK (extracellular-signal-regulated kinase) kinase]. MAPKAPK2 (MAPK-activated protein kinase-2) phosphorylated bacterially expressed full-length human Ago2 at serine-387 in vitro, but not the S387A mutant. Finally, mutation of serine-387 to an alanine residue or treatment of cells with a p38 MAPK inhibitor reduced the localization of Ago2 to processing bodies. These results suggest a potential regulatory mechanism for RNA silencing acting through Ago2 serine-387 phosphorylation mediated by the p38 MAPK pathway.

Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro

Science ◽  
1992 ◽  
Vol 257 (5075) ◽  
pp. 1404-1407 ◽  
Author(s):  
P Dent ◽  
W Haser ◽  
T. Haystead ◽  
L. Vincent ◽  
T. Roberts ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
3T3 Cells ◽  
Mitogen Activated Protein ◽  
Nih 3T3 ◽  
Protein Kinase Kinase ◽  
Nih 3T3 Cells

scholarly journals Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation

1994 ◽  
Vol 14 (3) ◽  
pp. 1594-1602
Author(s):  
A J Rossomando ◽  
P Dent ◽  
T W Sturgill ◽  
D R Marshak
Keyword(s):  
Protein Kinase ◽  
Phosphorylation Site ◽  
Mitogen Activated Protein Kinase ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Protein Kinase Cascade ◽  
Protein Kinase Kinase

Mitogen-activated protein kinase kinase 1 (MKK1), a dual-specificity tyrosine/threonine protein kinase, has been shown to be phosphorylated and activated by the raf oncogene product as part of the mitogen-activated protein kinase cascade. Here we report the phosphorylation and inactivation of MKK1 by phosphorylation on threonine 286 and threonine 292. MKK1 contains a consensus phosphorylation site for p34cdc2, a serine/threonine protein kinase that regulates the cell division cycle, at Thr-286 and a related site at Thr-292. p34cdc2 catalyzes the in vitro phosphorylation of MKK1 on both of these threonine residues and inactivates MKK1 enzymatic activity. Both sites are phosphorylated in vivo as well. The data presented in this report provide evidence that MKK1 is negatively regulated by threonine phosphorylation.

Inhibition of Mitogen Activated Protein Kinase Kinase (MEK1) Is Effective Against CLL Cells Cultured in Media Alone or in a Supportive Microenvironment and Is Synergistic with Fludarabine in a Mechanism That Involves Decreased Levels of Reactive Oxygen Species and MCL-1 Protein

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1804-1804
Author(s):  
Giles Best ◽  
Kyle Crassini ◽  
Williams Stevenson ◽  
Stephen P. Mulligan
Keyword(s):  
Reactive Oxygen Species ◽  
Clinical Trials ◽  
Protein Kinase ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Species ◽  
Mitogen Activated Protein ◽  
Cells Cultured ◽  
Protein Kinase Kinase

Abstract Abstract 1804 Background Despite the high response rates of patients with Chronic Lymphocytic Leukemia (CLL) to the fludarabine (F), cyclophosphamide (C), rituximab (R) regimen, relapsed or refractory disease is common. Novel therapeutic approaches are required that are effective in this setting. Targeting specific signaling molecules is proving an effective strategy for treating patients who are refractory to FCR. Given that the mitogen-activated protein kinase pathway (MAPK) pathway is constitutively active in CLL cells and that inhibitors of mitogen-activated protein kinase kinase (MEK1) in this pathway are in clinical trials for solid tumors, we sought to investigate the potential of MEK1 as a therapeutic target in CLL. Results Inhibition of MEK1/2 using MEK inhibitor I (MEKi; Calbiochem/Merck) induced apoptosis in the MEC1 cell line and in 18 patient samples. Importantly, sensitivity of the patient samples occurred irrespective of ATM/TP53 functional status, of poor prognostic features or of treatment history. MEKi was also effective against 4 CLL patient samples cultured in an in vitro model of the tumor microenvironment, albeit with a significantly higher IC50 than observed against CLL cells cultured in media alone. As fludarabine-based therapies have become the mainstay of CLL treatment, we investigated the effect of combining the MEK inhibitor with this purine analogue. Synergy between MEKi and fludarabine was apparent against the MEC-1 cell line and 10 patient samples. Dose reduction indices (DRI) calculated from the drug combination indicate this synergy was predominantly due to an increase in fludarabine sensitivity. Investigation of the mechanisms of the synergy between MEKi and fludarabine suggests decreased levels of reactive oxygen species (ROS) and expression of the pro-survival protein, MCL-1, may be contributing factors (see figure). Summary These data suggest for the first time that inhibition of MEK1/2 may represent a potential therapeutic option for CLL patients. The efficacy of the MEK inhibitor against CLL cells cultured in the supportive in vitro environment suggest that this approach may also be effective at targeting the proliferative fraction of CLL cells in the tumor microenvironment. As clinical trials of MEK1/2 inhibitors are currently underway in solid tissue malignancies, our data suggest that trials of these agents may also be warranted for high risk CLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Anti-Inflammatory Effects of Mitogen-Activated Protein Kinase Kinase Inhibitor U0126 in an Asthma Mouse Model

2004 ◽  
Vol 172 (11) ◽  
pp. 7053-7059 ◽  
Author(s):  
Wei Duan ◽  
Jasmine H. P. Chan ◽  
Chui Hong Wong ◽  
Bernard P. Leung ◽  
W. S. Fred Wong
Keyword(s):  
Protein Kinase ◽  
Mouse Model ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Asthma Mouse Model ◽  
Protein Kinase Kinase
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