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Global identification of genes and pathways regulated by Akt during activation of T helper cells

Kane, LP and Cheng, J (2013) Global identification of genes and pathways regulated by Akt during activation of T helper cells. F1000Research, 2. ISSN 2046-1402

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Abstract

© 2013 Cheng J et al. We previously demonstrated that Akt differentially modulated a subset of NF-kB target genes during T cell activation. In the current study, we further explored the broader effects of Akt inhibition on T cell gene induction. Global microarray analysis was used to characterize T helper cell transcriptional responses following antigen receptor stimulation in the absence or presence of Akti1/2 (an allosteric inhibitor which targets Akt1 and Akt2), to identify novel targets dependent upon Akt and obtain a more comprehensive view of Akt-sensitive genes in Th2 helper T cells. Pathway analysis of microarray data from a CD4 + Th2 T cell line revealed effects on gene networks involving ribosomal and T cell receptor signaling pathways associated with Akti1/2 treatment. Using real-time PCR analysis, we validated the differential regulation of several genes in these pathways, including Ier3, Il13, Egr1, Ccl1 and Ccl4, among others. Additionally, transcription factor target gene (TFactS) analysis revealed that NF-kB and Myc were the most significantly enriched transcription factors among Akt-dependent genes after T cell receptor and CD28 stimulation. Akt activation elicited increases in the enrichment of NF-kB- and Myc-targeted genes. The present study has identified a diverse set of genes, and possible mechanisms for their regulation, that are dependent on Akt during T cell activation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kane, LPlkane@pitt.eduLKANE
Cheng, JJIC15@pitt.eduJIC15
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
ReviewerFinlay, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
ReviewerBommhardt, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
ReviewerGold, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 May 2013
Date Type: Publication
Journal or Publication Title: F1000Research
Volume: 2
DOI or Unique Handle: 10.12688/f1000research.2-109.v2
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
ISSN: 2046-1402
Date Deposited: 09 Aug 2016 19:55
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29130

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