Journal
CELLULAR MICROBIOLOGY
Volume 10, Issue 9, Pages 1787-1800Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1462-5822.2008.01165.x
Keywords
-
Categories
Funding
- NIAID NIH HHS [R01 AI057831-04, R01 AI057831-05, R01 AI057831] Funding Source: Medline
Ask authors/readers for more resources
Interferon-gamma-inducible GTPase (IGTP) expression is upregulated in coxsackievirus B3 (CVB3)-infected murine heart and inhibits CVB3-induced apoptosis through activation of the PI3 kinase/Akt pathway. However, the mechanism of this pathway activation is unknown. In this study, using doxcycycline-inducible Tet-On HeLa cells that overexpress IGTP, we have demonstrated that focal adhesion kinase (FAK) is phosphorylated in response to IGTP expression and that transfection of the Tet-On HeLa cells with a dominant negative FAK (FRNK) blocks Akt activation. Furthermore, induction of IGTP also promoted the NF-kappa B activation as evidenced by its enhanced nuclear translocation, binding to transcriptional promoters and increased transcriptional activity. However, FRNK transfection and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 both blocked the IGTP-induced translocation and NF-kappa B activation. Furthermore, silencing NF-kappa B with siRNAs significantly inhibited the phosphorylation of FAK and Akt, but not their total expression levels, indicating that NF-kappa B activation is required for the IGTP-induced activation of FAK and PI3K/Akt. Finally, blocking this survival pathway by transfection of FRNK or silencing of NF-kappa B reduced CVB3 replication and enhanced cell death during CVB3 infection. Taken together, these results suggest that FAK is a mediator upstream of PI3K/Akt and NF-kappa B functions as a downstream effector and also positively regulates the activity of upstream kinases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available