scholarly journals Stimulation of 92-kDa Gelatinase B Promoter Activity byrasIs Mitogen-activated Protein Kinase Kinase 1-independent and Requires Multiple Transcription Factor Binding Sites Including Closely Spaced PEA3/etsand AP-1 Sequences

1996 ◽  
Vol 271 (18) ◽  
pp. 10672-10680 ◽  
Author(s):  
Rebecca Gum ◽  
Ernst Lengyel ◽  
Jose Juarez ◽  
Ji Hshiung Chen ◽  
Hiroshi Sato ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Binding Sites ◽  
Promoter Activity ◽  
Transcription Factor Binding Sites ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Multiple Transcription Factor ◽  
Stimulation Of ◽  
Protein Kinase Kinase

VEGFD regulates blood vascular development by modulating SOX18 activity

Blood ◽  
2014 ◽  
Vol 123 (7) ◽  
pp. 1102-1112 ◽  
Author(s):  
Tam Duong ◽  
Katarzyna Koltowska ◽  
Cathy Pichol-Thievend ◽  
Ludovic Le Guen ◽  
Frank Fontaine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Vascular Development ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Key Points ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Key Points Haploinsufficiency of Sox18 reveals an important role for VEGFD in regulating blood vascular development in vivo in vertebrates. VEGFD acts through mitogen-activated protein kinase kinase–extracellular signal-regulated kinase to modulate the activity and nuclear concentration of endothelial-specific transcription factor SOX18.

scholarly journals Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation of the TAL1/SCL transcription factor in murine proerythroblasts

1999 ◽  
Vol 343 (3) ◽  
pp. 615-620 ◽  
Author(s):  
Tong TANG ◽  
K. S. Srinivasa PRASAD ◽  
Mark J. KOURY ◽  
Stephen J. BRANDT
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Erythroid Differentiation ◽  
Signalling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Friend Virus ◽  
Phosphatidylinositol 3 Kinase ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Ectopic expression of the basic helix-loop-helix transcription factor TAL1 (or SCL) is the most frequent gain-of-function mutation in T-cell acute lymphoblastic leukaemia. Gene-knockout studies in mice have demonstrated that TAL1 is required for embryonic and adult haematopoiesis, and considerable evidence suggests it also has important functions in terminal erythroid differentiation. We reported previously that TAL1 phosphorylation is stimulated by erythropoietin in splenic proerythroblasts isolated from mice infected with the anaemia-inducing strain of Friend virus and show here the signalling pathway responsible. Erythropoietin was found to stimulate nuclear mitogen-activated protein kinase activity in addition to TAL1 protein phosphorylation, both of which were quantitatively inhibited by the mitogen-activated protein kinase kinase inhibitor PD 098059 and the phosphatidylinositol 3-kinase inhibitor wortmannin. Tryptic phosphopeptide analysis of radiolabelled TAL1 immunoprecipitated from nuclear extracts of Friend virus-induced proerythroblasts revealed that phosphorylation of Ser122, shown previously to be a substrate for the mitogen-activated protein kinase ERK1 (extracellular signal-regulated protein kinase) in vitro, was specifically, although not exclusively, increased by erythropoietin and inhibited by wortmannin and PD 098059. These results are consistent with an erythropoietin-stimulated signalling pathway in which there is direct activation of a mitogen-activated protein kinase kinase by phosphatidylinositol 3-kinase and identify TAL1 as one of its nuclear targets. These data suggest, in addition, a specific mechanism by which the principal regulator of erythroid differentiation could enhance TAL1 function, in addition to increasing its expression.

scholarly journals p38 Mitogen-Activated Protein Kinase-Dependent Activation of Protein Phosphatases 1 and 2A Inhibits MEK1 and MEK2 Activity and Collagenase 1 (MMP-1) Gene Expression

2001 ◽  
Vol 21 (7) ◽  
pp. 2373-2383 ◽  
Author(s):  
Jukka Westermarck ◽  
Song-Ping Li ◽  
Tuula Kallunki ◽  
Jiahuai Han ◽  
Veli-Matti Kähäri
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Promoter Activity ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Metalloproteinase 1 ◽  
Mitogen Activated Protein ◽  
Stimulation Of ◽  
Constitutively Active

ABSTRACT Degradation of collagenous extracellular matrix by collagenase 1 (also known as matrix metalloproteinase 1 [MMP-1]) plays a role in the pathogenesis of various destructive disorders, such as rheumatoid arthritis, chronic ulcers, and tumor invasion and metastasis. Here, we have investigated the role of distinct mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-1 gene expression. The activation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (designated ERK1,2) pathway by oncogenic Ras, constitutively active Raf-1, or phorbol ester resulted in potent stimulation of MMP-1 promoter activity and mRNA expression. In contrast, activation of stress-activated c-Jun N-terminal kinase and p38 pathways by expression of constitutively active mutants of Rac, transforming growth factor β-activated kinase 1 (TAK1), MAPK kinase 3 (MKK3), or MKK6 or by treatment with arsenite or anisomycin did not alone markedly enhance MMP-1 promoter activity. Constitutively active MKK6 augmented Raf-1-mediated activation of the MMP-1 promoter, whereas active mutants of TAK1 and MKK3b potently inhibited the stimulatory effect of Raf-1. Activation of p38 MAPK by arsenite also potently abrogated stimulation of MMP-1 gene expression by constitutively active Ras and Raf-1 and by phorbol ester. Specific activation of p38α by adenovirus-delivered constitutively active MKK3b resulted in potent inhibition of the activity of ERK1,2 and its upstream activator MEK1,2. Furthermore, arsenite prevented phorbol ester-induced phosphorylation of ERK1,2 kinase-MEK1,2, and this effect was dependent on p38-mediated activation of protein phosphatase 1 (PP1) and PP2A. These results provide evidence that activation of signaling cascade MKK3-MKK3b→p38α blocks the ERK1,2 pathway at the level of MEK1,2 via PP1-PP2A and inhibits the activation of MMP-1 gene expression.

Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) mediates the LH-induced stimulation of progesterone synthesis in the porcine corpus luteum

2019 ◽  
Vol 31 (9) ◽  
pp. 1444
Author(s):  
Di Zhang ◽  
Ying Liu ◽  
Yan Cui ◽  
Sheng Cui
Keyword(s):  
Protein Kinase ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Luteal Cells ◽  
Mitogen Activated Protein ◽  
Porcine Luteal Cells ◽  
Stimulation Of ◽  
Protein Kinase Kinase

Progesterone (P4) synthesized by the corpus luteum (CL) plays a key role in the establishment and maintenance of pregnancy. The LH signal is important for luteinisation and P4 synthesis in pigs. In a previous study, we demonstrated that mitogen-activated protein kinase kinase kinase 8 (MAP3K8) regulates P4 synthesis in mouse CL, but whether the function and mechanism of MAP3K8 in the pig is similar to that in the mouse is not known. Thus, in the present study we investigated the effects of MAP3K8 on porcine CL. Abundant expression of MAP3K8 was detected in porcine CL, and, in pigs, MAP3K8 expression was higher in mature CLs (or those of the mid-luteal phase) than in regressing CLs (late luteal phase). Further functional studies in cultured porcine luteal cells showed that P4 synthesis and the expression of genes encoding the key enzymes in P4 synthesis are significantly reduced when MAP3K8 is inhibited with the MAP3K8 inhibitor Tpl2 kinase inhibitor (MAP3K8i, 10μM). After 12–24h treatment of luteal cells with 100ngmL−1 LH, MAP3K8 expression and P4 secretion were significantly upregulated. In addition, the 10μM MAP3K8 inhibitor blocked the stimulatory effect of LH on P4 synthesis and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in porcine luteal cells. The LH-induced increases in MAP3K8 phosphorylation and expression, ERK1/2 phosphorylation and P4 synthesis were all blocked when protein kinase A was inhibited by its inhibitor H89 (20 μM) in porcine luteal cells. In conclusion, MAP3K8 mediates the LH-induced stimulation of P4 synthesis through the PKA/mitogen-activated protein kinase signalling pathway in porcine CL.

scholarly journals Constitutive Activation of the Fission Yeast Pheromone-Responsive Pathway Induces Ectopic Meiosis and Reveals Ste11 as a Mitogen-Activated Protein Kinase Target

2005 ◽  
Vol 25 (5) ◽  
pp. 2045-2059 ◽  
Author(s):  
Søren Kjærulff ◽  
Inger Lautrup-Larsen ◽  
Søren Truelsen ◽  
Morten Pedersen ◽  
Olaf Nielsen
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Fission Yeast ◽  
Mitogen Activated Protein Kinase ◽  
Alternative Mechanism ◽  
Epistasis Analysis ◽  
Mitogen Activated Protein ◽  
Direct Target ◽  
Protein Kinase Kinase

ABSTRACT In the fission yeast Schizosaccharomyces pombe, meiosis normally takes place in diploid zygotes resulting from conjugation of haploid cells. In the present study, we report that the expression of a constitutively activated version of the pheromone-responsive mitogen-activated protein kinase kinase kinase (MAP3K) Byr2 can induce ectopic meiosis directly in haploid cells. We find that the Ste11 transcription factor becomes constitutively expressed in these cells and that the expression of pheromone-responsive genes no longer depends on nitrogen starvation. Epistasis analysis revealed that these conditions bypassed the requirement for the meiotic activator Mei3. Since Mei3 is normally needed for inactivation of the meiosis-repressing protein kinase Pat1, this finding suggests that the strong Byr2 signal causes inactivation of Pat1 by an alternative mechanism. Consistent with this possibility, we found that haploid meiosis was dramatically reduced when Ste11 was mutated to mimic phosphorylation by Pat1. The mutation of two putative MAPK sites in Ste11 also dramatically reduced the level of haploid meiosis, suggesting that Ste11 is a direct target of Spk1. Supporting this, we show that Spk1 can interact physically with Ste11 and also phosphorylate the transcription factor in vitro. Finally, we demonstrate that ste11 is required for pheromone-induced G1 arrest. Interestingly, when we mutated Ste11 in the sites for Pat1 and Spk1 phosphorylation simultaneously, the cells could still arrest in G1 in response to pheromone, suggesting the existence of yet a third bifurcation of the signaling pathway.

scholarly journals Mitogen-activated Protein Kinase Kinase Inhibition Does Not Block the Stimulation of Glucose Utilization by Insulin

1995 ◽  
Vol 270 (35) ◽  
pp. 20801-20807 ◽  
Author(s):  
Dan F. Lazar ◽  
Russell J. Wiese ◽  
Matthew J. Brady ◽  
Cynthia Corley Mastick ◽  
Steven B. Waters ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Utilization ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Inhibition ◽  
Mitogen Activated Protein ◽  
Stimulation Of ◽  
Protein Kinase Kinase
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