Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)

2018 ◽  
Vol 501 (2) ◽  
pp. 365-373 ◽  
Author(s):  
Xiao-Fan Xu ◽  
Fang Liu ◽  
Jia-Qi Xin ◽  
Jian-Wei Fan ◽  
Nan Wu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Transforming Growth Factor Β1 ◽  
Mitogen Activated Protein Kinase ◽  
Pancreatic Stellate Cell ◽  
Mitogen Activated Protein ◽  
Tgf Β1

scholarly journals MEK1/2 Inhibitors Block Basal and Transforming Growth Factor β1-Stimulated JC Virus Multiplication

2007 ◽  
Vol 81 (12) ◽  
pp. 6412-6418 ◽  
Author(s):  
Veerasamy Ravichandran ◽  
Peter N. Jensen ◽  
Eugene O. Major
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Jc Virus ◽  
Transforming Growth Factor Β1 ◽  
Virus Multiplication ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Tgf Β1

ABSTRACT The multiplication of the human neurotropic polyomavirus JC virus (JCV) is regulated by cell membrane receptors and nuclear transcription factors. Signaling pathways also play a role in determining the extent to which JCV can productively infect cells. These data show that constitutively active MEK1 protein (CA-MEK1), overexpressed in cultures of human glia, supports a substantial increase in late JCV protein (Vp-1) synthesis. The specificity of this pathway was indicated by no significant enhancement of JCV multiplication through activation of other components of mitogen-activated protein kinase pathways such as p38, Jun N-terminal protein kinase, and protein kinase A. Further evidence supporting the importance of signaling in JCV infection came from addition of transforming growth factor β1 (TGF-β1), which stimulated a 200% increase of Vp-1 expression. Specific MEK1/2 inhibitors, flavenoid PD98059 and U0126, decreased the basal and TGF-β1-stimulated Vp-1 expression by 95% or more. TGF-β1 is known to phosphorylate/activate Smad DNA binding proteins that could subsequently bind or increase binding to JCV promoter sequences, linking the effects of signaling with JCV transcriptional regulation. The effectiveness with which MEK1/2 inhibitors block JCV multiplication provides insight that may contribute to development of compounds directed against JCV.

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