Figure 2. PI3K pathway in TLR signaling.
PI3K physically interacts with multiple TLRs as well as MyD88. Activated PI3K regulates TLR signaling in both positive and negative ways. Inactivation of GSK3 by PI3K-Akt enhances the transcription of IL10 by allowing CREB DNA binding as well as CREB-CBP association. IL-12 transcription is inhibited due to decreased association of NF-kB with CBP. PI3K-Akt also phosphorylates mTOR which leads to the phosphorylation and activation of IRF-7 as well as enhanced production of type I IFNs. PI3K-Akt pathway is also involved in cell proliferation or survival induced by multiple TLR ligands through degradation of the cell cycle inhibitor p27.