Akt2 inhibits the activation of NFAT in lymphocytes by modulating calcium release from intracellular stores

Victoria A. Martin, Wen Horng Wang, Andrew M. Lipchik, Laurie L. Parker, Yantao He, Sheng Zhang, Zhong Yin Zhang, Robert L. Geahlen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The engagement of antigen receptors on lymphocytes leads to the activation of phospholipase C-γ, the mobilization of intracellular calcium and the activation of the NFAT transcription factor. The coupling of antigen receptors to the activation of NFAT is modulated by numerous cellular effectors including phospho-inositide 3-kinase (PI3K), which is activated following receptor cross-linking. The activation of PI3K has both positive and negative effects on the receptor-mediated activation of NFAT. An increase in the level and activity of Akt2, a target of activated PI3K, potently inhibits the subsequent activation of NFAT. In contrast, an elevation in Akt1 has no effect on signaling. Signaling pathways operating both upstream and downstream of inositol 1,4,5-trisphosphate (IP3)-stimulated calcium release from intracellular stores are unaffected by Akt2. An increase in the level of Akt2 has no significant effect on the initial amplitude, but substantially reduces the duration of calcium mobilization. The ability of Akt2 to inhibit prolonged calcium mobilization is abrogated by the administration of a cell permeable peptide that blocks the interaction between Bcl-2 and the IP3 receptor. Thus, Akt2 is a negative regulator of NFAT activation through its ability to inhibit calcium mobilization from the ER.

Original languageEnglish (US)
Pages (from-to)1064-1073
Number of pages10
JournalCellular Signalling
Issue number5
StatePublished - May 2012

Bibliographical note

Funding Information:
This research was supported by National Institutes of Health Grants CA037372 (RLG), CA127161 (LLP) and CA152194 (ZYZ) awarded by the National Cancer Institute.


  • Akt
  • B cell signaling
  • Bcl-2
  • Calcium mobilization
  • IP3 receptor
  • NFAT


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