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

► Akt negatively regulates the activation of NFAT through the B cell antigen receptor. ► Akt2, but not Akt1, inhibits antigen receptor-mediated activation of NFAT. ► Akt2 fails to block signaling upstream or downstream of calcium release from the ER. ► Akt2 inhibits sustained calcium release from the endoplasmic reticulum. ► Inhibition by is reversed by blocking Bcl-2 binding to the IP3 receptor.