|
KMID : 0624620140470120685
|
|
BMB Reports
2014 Volume.47 No. 12 p.685 ~ p.690
|
|
|
Constitutively active Ras negatively regulates Erk MAP kinase through induction of MAP kinase phosphatase 3 (MKP3) in NIH3T3 cells
|
|
Park Young-Jae
Lee Jong-Min
Shin Soon-Young
Kim Young-Ho
|
|
|
Abstract
|
|
|
|
The Ras/Raf/MEK/Erk signaling pathway is important for regulation of cell growth, proliferation, differentiation, survival, and apoptosis in response to a variety of extracellular stimuli. Lack of Erk MAPK activation is observed in several cancer cells despite active activation of Ras. However, little is known about the modulation of Erk1/2 activity by active Ras. Here, we show that overexpression of active H-Ras (H-RasG12R) in NIH3T3 fibroblasts impaired FGF2-induced Erk1/2 phosphorylation, as compared to wild-type cells. Northern blot analysis revealed that prolonged expression of active Ras increased MAP kinase phosphatase 3 (MKP3) mRNA expression, a negative regulator of Erk MAPK. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway abrogated active Ras-induced up-regulation of MKP3 expression, leading to the rescue of Erk1/2 phosphorylation. Our results demonstrated that the Ras/Raf/MEK/Erk signaling cascade is negatively regulated by the PI3K/Aktdependent transcriptional activation of the MKP3 gene.
|
|
|
KEYWORD
|
|
|
Active H-Ras, Mitogen-activated protein kinase, Mitogen-activated protein kinase phosphatase 3, NIH3T3 fibroblast, Phosphatidylinositol 3-kinase
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|